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Número de publicaciónWO2001039682 A1
Tipo de publicaciónSolicitud
Número de solicitudPCT/US1999/028570
Fecha de publicación7 Jun 2001
Fecha de presentación2 Dic 1999
Fecha de prioridad2 Dic 1999
También publicado comoCA2392642A1, EP1235526A1
Número de publicaciónPCT/1999/28570, PCT/US/1999/028570, PCT/US/1999/28570, PCT/US/99/028570, PCT/US/99/28570, PCT/US1999/028570, PCT/US1999/28570, PCT/US1999028570, PCT/US199928570, PCT/US99/028570, PCT/US99/28570, PCT/US99028570, PCT/US9928570, WO 0139682 A1, WO 0139682A1, WO 2001/039682 A1, WO 2001039682 A1, WO 2001039682A1, WO-A1-0139682, WO-A1-2001039682, WO0139682 A1, WO0139682A1, WO2001/039682A1, WO2001039682 A1, WO2001039682A1
InventoresDon Bobo, Jr.
SolicitanteBaxter International Inc.
Exportar citaBiBTeX, EndNote, RefMan
Enlaces externos:  Patentscope, Espacenet
Methods and apparatus for delivering medicament to tissue
WO 2001039682 A1
Resumen
A system for delivering medicaments to tissue includes a tissue-removal and medicament-delivery device. The device includes a delivery member and an optical fiber formed together into a unitary structure by cladding. The optical fiber has an inlet for receiving laser energy from a laser energy source and an outlet for emitting laser energy. The delivery member has an inlet for receiving medicament from a medicament source and an outlet for injecting medicament. A handpiece is adapted to receive the ablating and injecting device in a controlled and movable relationship. In use, a distal end of the handpiece is placed against tissue to be ablated. The ablating and injecting device is advanced beyond the distal end of the handpiece and into the tissue while emitting laser energy from the optical fiber. The emitted laser energy ablates the tissue as the optical fiber advances. The ablating and injecting device is then retracted from the tissue, thereby resulting in a channel formed in the tissue. While the device retracts, medicament is injected from the delivery member into the channel, thereby providing a plug within the channel. Alternatively, medicament may be injected into the tissue surrounding the channel by delivering the medicament into the tissue surrounding the channel opening or delivering it directly into the channel wall. The medicament may include growth factor combined with a cellular matrix which enhances angiogenesis in the tissue or may include a gene that encodes for said growth factor, or any other therapeutic agent or gene therapy agent that promotes angiogenesis or any therapeutic agent for the treatment of cardiovascular disease. The medicament delivery system is particularly useful in cardiac applications for performing transmyocardial revascularization (TMR) in ischemic myocardium and promoting endothelial cell growth within the myocardium.
Reclamaciones  (El texto procesado por OCR puede contener errores)
CLA I M S
What is claimed is
1 A medicament delivei y system compnsing A) a laser source for pi ovidmg lasei enei gy, B) a medicament source foi pi ovidmg medicament, C) an ablating and delivei mg device including (1 ) an optical fibei having (a) a distal portion, (b) an let end foi coupling to said lasei soui ce, and (c) an outlet end disposed at said distal portion foi emitting lasei enei gy, and (2) a delivery membei having (a) a lumen, (b) a distal portion, (c) an inlet end foi coupling to said medicament soui ce, and (d) an outlet end disposed at said distal portion foi injecting medicament, and D) a handpiece w hich i eceives said ablating and injecting device in conti oiled movable relationship thei eto
2 A medicament deliver, system as claimed in claim 1 vvhei em said ablating and injecting device fui thei includes cladding disposed about said distal portions of said optical fibei and said deliveiy membei , ther eby foi ming an mtegi al distal portion of said ablating and delivering device
3 A medicament delivei \ system as claimed m claim 2 whei ei said handpiece reciprocates said distal portion of said ablating and injecting dev ice between an advanced position and a retracted position
4 A medicament deliveiy system as claimed in claim 3 fui thei compnsing a conti ol unit connected to said lasei soui ce and said medicament soui ce
5. A medicament deliveiy system as claimed in claim 4 wherein said control unit activates said laser source to emit laser energy when said distal portion of said ablating and injecting device moves from said retracted position to said advanced position
6. A medicament delivery system as claimed in claim 5 wherein said control unit activates said medicament source to inject medicament when said distal portion of said ablating and injecting device moves from said advanced position to said retracted position
7 Apparatus for use in delivering medicament to tissue, comprising an ablating and delivering device including ( 1 ) an optical fiber having (a) a distal portion, (b) an inlet end for coupling to a laser energy source, and (c) an outlet end disposed at said distal portion for emitting laser energy; and (2) a deliveiy member having (a) a lumen, (b) a distal portion, (c) an inlet end for coupling to a medicament source, and (d) an outlet end disposed at said distal portion for providing medicament
8 Apparatus as claimed in claim 7 further comprising a handpiece which receives said ablating and delivering device in controlled, movable relationship thereto
9 A method for delivering medicament to tissue, said method comprising the steps of providing access to the tissue, forming a channel in the tissue by removing tissue, and providing medicament in said channel and/or in tissue surrounding said channel
10. A method as claimed in claim 9 wherein said forming step comprises the step of ablating the tissue with laser energy
1 1 A method as claimed in claim 9 wherein said forming step comprises the step of converting the tissue to gas with high-frequency electrical energy
12 A method as claimed in claim 9 wheiem said step of providing medicament comprises the step of providing growth factoi
13 A method as claimed in claim 12 wheiem said step of providing giowth factor comprises the step of providing giowth factor combined ith a cellular matiix
14 A method as claimed in claim 12 wheiem said step of piovidmg growth factoi comprises the step of providing giowth factoi combined with fibiin
15 A method as claimed m claim 12 wheiem said step of piovidmg giowth factor comprises the step of piovidmg growth factor combined with collagen
16 A method as claimed in claim 12 wheiem said step of piovidmg giowth factoi comprises the step of providing growth factoi in an atomi ed foim
17 A method as claimed in claim 9 wheiem said step of piovidmg medicament comprises the step of providing medicament pneumatically
IS A method as claimed in claim 9 wheiem said step of piovidmg medicament comprises the step of piovidmg medicament hydιaulιcall\
19 A method as claimed in claim 9 wheiem the tissue is myocardium, said forming step compnsing the step of foiming a channel completely through the myocardium
20 A method as claimed in claim 9 wheiem the tissue is myocaidium, said forming step comprising the step of forming a channel partially through the myocardium.
21. A method as claimed in claim 9 wherein said step of providing a medicament comprises the step of: providing a medicament to tissue surrounding said channel.
22. A system for delivering medicament to tissue, comprising: a tissue-removal device for forming a channel in the tissue, a delivery member for delivering medicament to and/or adjacent to said channel, said delivery member including a lumen with an inlet for receiving medicament and an outlet for providing medicament; and a handpiece that receives said delivery member so that said outlet is positionable to deliver medicament to said channel.
23. A system as claimed in claim 22 wherein said tissue-removal device includes an optical fiber.
24. A system as claimed in claim 22 wherein said tissue-removal device includes an electrode for emitting high-frequency electrical energy.
25. A system as claimed in claim 22 further including cladding for forming said tissue- removal device and said deliveiy member into a substantially unitary structure.
26. A system for delivering medicament to tissue, comprising: a tissue-removing mechanism which removes tissue to form a channel in the tissue; and a delivery conduit mechanism which moves medicament from a source to said channel.
27. A system as claimed in claim 26 wherein said tissue-removing mechanism removes tissue with laser energy.
28. A system as claimed in claim 26 wherein said tissue-removing mechanism removes tissue with electrical energy.
3 -
29 A system as claimed in claim 26 whei em said deliveiy conduit mechanism includes a lumen with an inlet for receiving medicament fi om a soui ce and an outlet for providing medicament to said channel
30 A method foi deliver ing medicament to tissue, said method compnsing the steps of selecting tissue to l eceive medicament accessing the selected tissue, stimulating a natural response in the selected tissue, and providing medicament to the selected tissue
3 1 A method as claimed in claim 30 w hei em said selecting step comprises the step of selecting caidiac tissue
32 A method as claimed in claim 3 1 whei em said selecting step compnses the step of selecting ischemic cardiac tissue
33 A method as claimed in claim 32 whei em said stimulating step comprises the step of stimulating an angiogenic I espouse in the ischemic cai diac tissue
34 A method as claimed in claim 33 whei em said pi ovidmg step compnses the step of pr oviding growth factoi to the cai diac tissue
35 A method as claimed in claim 3 1 whei em said stimulating step compnses the step of ablating the selected tissue with lasei eneι g\
3b
36 A method as claimed in claim 35 wherein said ablating step comprises the step of ablating the selected tissue to form a hole or channel therein
37 A method as claimed in claim 36 wherein said providing step comprises the step of. providing medicament to said hole or channel
38 A method as claimed in claim 36 wherein said providing step comprises the step of providing medicament to tissue suπ oundmg said hole or channel
39 A method as claimed in claim 3 1 wherein said stimulating step comprises the step of: subjecting the selected tissue to high-frequency electrical energy
40 A method as claimed in claim 3 1 wherein said providing step comprises the step of providing growth factor
41 A medicament delivery system comprising an energy source for providing energy to remove tissue, a medicament source for providing medicament to the tissue, an energy transmitting member having a an inlet end for coupling to said energy source and an outlet end disposed at a distal portion for emitting energy, a medicament delivery member having an inlet end for coupling to said medicament source, at least one lumen through said delivery member for delivering medicament, a distal portion terminating in a tissue-engaging surface having ports in fluid communication with said lumen for injecting medicament directly into the tissue, and a handpiece which receives said energy transmitting member and said medicament deliveiy member
42. The medicament delivery system of claim 4 I wherein said tissue-engaging surface further comprises one or more needles in fluid communication with said lumen for piercing the tissue and injecting medicament directly into the tissue
43 The medicament deliv ei y system of claim 4 I whei em said tissue-engaging surface further comprises one oi moi e nozzles in fluid communication with said lumen for injecting medicament dn ectly into the tissue
44 The medicament delivery system of claim 41 wherein said eneigy soui ce comprises a soui ce of lasei eneigy and said eneig1, ti ansmittmg membei compnses an optical fiber
45 The medicament delivei y system of claim 4 1 whei em said eneigy transmitting membei comprises an electrode for emitting high-fi equency electrical energy
46 A medicament delivei y system compnsing an enei gy soui ce for pi ovidmg enei gy to r emov e tissue a medicament soui ce foi pi ovidmg medicament to the tissue a vacuum soui ce foi pr oviding vacuum to the system, and an enei gy transmitting and medicament delivei y membei having a an inlet end for coupling to said energy source, said medicament soui ce and said vacuum source and an outlet end disposed at a distal portion foi emitting enei gy and delivering medicament, said enei gy ti ansmittmg and medicament deliveiy membei further comprising at least a first vacuum lumen in communication with said vacuum source and at least a first medicament deliveiy lumen in fluid communication with said medicament source, and at least two ports pi oximal to said distal portion and in close pi oximity to each other , comprising at least a fu st vacuum port in fluid communication with said vacuum lumen for providing vacuum to the tissue and at least a fu st deliv eiy port is in fluid communication with said medicament deliveiy lumen foi injecting medicament directly into the tissue
47 The medicament delivei y system of claim 46 further compnsing a second vacuum lumen in communication with said vacuum source, a second medicament deliveiy lumen in fluid communication with said medicament source, a second vacuum port in fluid communication with said second vacuum lumen foi providing vacuum to the tissue, and a second deliveiy port in fluid communication with said medicament deliveiy lumen for injecting medicament directly into the tissue
48 The medicament deliveiy system of claim 47 wherein said delivery ports are substantially diametrically opposed to each othei on the delivery member
49 The medicament deliveiy system of claim 47 wherein said vacuum ports are substantially diametπcally opposed to each othei on the deliveiy membei
50 The medicament deliveiy system of claim 46 whei em said energy transmitting and medicament deliveiy membei fui thei compnses a distal portion having a tissue- engaging suiface wherein said lumens and said ports tei minate foi pi ovidmg vacuum and medicament delivery to the tissue
51 A medicament injection unit compnsing an injection jet nozzle, a medicament soui ce foi pi ovidmg medicament to the tissue and in fluid communication with said nozzle, and a pressuie source in fluid communication w ith said nozzle and said medicament source
52 A method of delivei mg medicament to tissue, said method compnsing the steps of, piovidmg an injection jet nozzle coupled to a soui ce of fluid and coupled to a source of medicament, delivering said fluid thi ough said noz le w ith sufficient pi essui e to foi m a hole in oi through the tissue, providing a source of high piessui e between said soui ce of medicament and said jet nozzle to create a fluid column of medicament foi injection into the tissues, and delivering medicament to the tissue thiough said jet nozzle
53 , A method of deliver mg medicament to tissue, said method comprising the steps of, pi ovidmg an injection jet nozzle coupled to a soui ce of fluid and coupled to a source of medicament, providing a source of high pi essui e between said soui ce of medicament and said jet nozzle to create a fluid column of medicament foi injection into the tissues, delivering said fluid through said nozzle with sufficient pressure to form a hole in or through the tissue while delivering medicament to the tissue through said jet nozzle to the tissue.
54. A method of delivering medicament to tissue, said method comprising the steps of: providing access to the tissue; forming a channel in the tissue by removing tissue; and providing medicament directly to the tissue surrounding said channel.
55. The method of claim 54 further comprising the step of providing medicament directly to the tissue surrounding the opening of the channel.
56. The method of claim 55 further comprising the step of piercing the tissue surrounding the opening of the channels and injecting medicament into the tissue.
57. The method of claim 54 further comprising the step of providing medicament directly to the tissue surrounding said by delivering medicament directly to the tissue comprising the channel wall.
Descripción  (El texto procesado por OCR puede contener errores)

METHODS AND APPARATUS FOR DELIVERING MEDICAMENT TO TISSUE

FIELD OF THE INVENTION

The present invention is directed to surgical methods and apparatus for delivering medicament to tissue More particularly, the present invention is directed to surgical methods and apparatus for delivering medicament to tissue by first removing tissue to form a hole or channel in the tissue and then delivering medicament into the hole or channel or into the tissue surrounding the hole or channel. The methods and apparatus of the present invention may be applied in delivering growth factor to cardiac tisstie during transmyocardial revascularization

BACKGROUND OF TH E INVEN ION Cardiomyopathy (cardto meaning "heart" and niyopathy meaning "muscle disease") refers to a group of disorders that directly damage the muscle of the heart walls, or myocardium. In these disorders, all chambers of the heart are affected The heart's function as a pump is disaipted, leading to an inadequate blood flow to organs and tissues of the body Depending on the nature of the injury or abnormality in the heart muscle and the resulting structural changes in the heart chambers, one of thi ee types of nonischeniic (that is, not caused by heart attack) heart muscle disease may be present in a patient dilated congestive, hypertrophic, or restrictive

Dilated congestive cardiomyopathy damages the fibers of the heart muscle, weakening the walls of the heart's chambers The chambers thereby lose some of their capacity to contract forcefully and pump blood through the circulatory system To compensate for the muscle injury, the heart chambers enlarge or dilate which causes heart failure Hypertrophic cardiomyopathy is characterized by a disorderly growth of heart muscle fibers causing the heart chambers to become thick walled and bulky The thickening is generally most striking in the walls of the left ventricle, the chamber of the heart which pumps blood through the aorta to the vital organs and tissues of the body The distorted left ventricle contracts, but the supply of blood to the brain and other vital organs may be inadequate because blood is trapped within the heart during contractions Restrictive cardiomyopathy causes abnormal cells, proteins, or scai tissue to infiltrate the muscle and structures of the heart, causing the chambers to become stiff and bulky The heart may initially contract normally, but the ngid chambers restrict the return of blood to the heart

Massive or multiple heart attacks may also lead to sevei e heart damage as a l esult of a disruption of blood supply to heart muscle The damage can result in functional impairment and structural abnormalities similar to those found in the other types of cardiomyopathy This type of heart disease, resulting fiom coronary artery disease, is called lschenuc cu iomyopalln

(ischemic meaning "lacking oxygen")

Severe heart injury caused by a major heart attacks or multiple smaller heart attacks ma> result in heart enlargement and thinning of the chambei walls, abnormalities which resemble those observed in dilated caidiomyopathy Ischemic caidiomyopathy typically develops in patients with severe coi onary artery disease, often complicated by othei conditions such as diabetes and hypertension

Although heart failui e symptoms in ischemic caι

opathy ai e similar to those found in dilated cardiomyopathy, ischemic disease is more likely to be accompanied by symptoms of coronary artery disease, such as angina (which is chest pain i esulting from reduced oxygen supply to the heart muscle) Diagnosis is typically based on a history of heart attacks and studies that demonstrate poor function in major portions of the left ventricle The diagnosis can be confirmed by coronary angiography, which re\ eals ai eas of nan owing and blockage in the coronary blood vessels Patients with ischemic caι dιom\opathy ai e ti eated with medications that i elieve heart failure symptoms and impi ov e blood flow thi ough the diseased coi onaiy arteries such as nitroglyceπn, some types of calcium channel blockei , and angiotensin-conveitmg enzyme

(ACE) inhibitors When symptoms of heart failui e and coronaiy artery disease cannot be controlled with medications, coronaiy angioplasty oi suigeiy may be co sideied Angioplasty and coronaiy artery bypass gi afting may help inci ease blood flow to the heart which in tui n enhances heart muscle function

When heart failure symptoms ai e advanced and cannot be impi oved by di ug theι p oi surgery, patients may be refei red foi a heart ti anspla t Patients with ischemic caι dιom> opath\ account for approximately one half of all heart ti ansplant recipients With a limited supply of donor hearts and complications resulting fiom heart transplant (such as organ rejection), surgeons have been exploring alternative pi ocedures for ti eating severe ischemic

_ i _ cardiomyopathy. One such procedure is Iransinyoctirdial revasciilarizctlioii, otherwise known more simply as "TMR."

TMR procedures revascularize, that is, form new channels, in the heart muscle or myocardium. The newly formed channels penetrate through the entire heart wall, which includes the epicardiiim (the outer layer of the heart), the endocardium (the inner lining of the heart), and the myocardium or muscular wall therebetween. As ischemic cardiomyopathy more often than not afflicts the left ventricle, the new channels are typically formed in the heart wall of this chamber of the heart. Accordingly, oxygenated blood from the lungs present in the left ventricle awaiting to be pumped through the aorta is able to flow directly into the newly formed channels to nourish the heart muscle.

Pioneering methods for performing TMR involved the use of needles for physically puncturing holes in the heart wall. These methods resulted in only a temporary delivery of blood to the myocardium because the holes quickly healed at the endocardium, preventing oxygenated blood from entering the myocardium One of the more recent and exciting methods of performing TMR is through the use of lasers. It has been observed that new holes or channels formed in the heart wall by a laser tend to heal at the epicardiiim, which prevents blood loss, and promote blood perfusion into the ischemic region of the myocardium.

Lasers have proven to be a widely useful and applicable tool in modern medical techniques, particularly in minimally invasive surgical procedures. Technically speaking, a laser (the word laser being an acronym for /ight amplification by .stimulated emission of /'adiation) utilizes the natural oscillations of atoms or molecules between energy levels for generating coherent electromagnetic radiation. A laser is able to produce high-intensity and high-energy light at a single frequency. The energy of laser light is measured in joules (J), or watt-seconds (W-s), and the power of a laser is measured in watts (W). One of the conventional surgical apparatus for performing TMR consists of a laser and an optical fiber. A surgeon places the end of the optical fiber against the epicardiiim to ensure that all the laser light is focused at the desired point, and then the laser is fired In order to form the new channel completely through the heart wall and into the chamber, the surgeon needs to tactilely urge the optical fiber into and through the epicardiiim, the myocardium, and the endocardium. Because of the nature of ischemic cardiomyopathy, the thickness of the diseased myocardium is irregular and greater than normal. Accordingly, the surgeon needs to tactilely urge the optical fiber through the heart wall at each location. This procedure takes a certain amount of time to accomplish safely and involves a certain amount of guesswork on the part oϊ' the surgeon. This procedure is complicated by the beating of the heart. Accordingly, the firing of the laser needs to be synchronized with the beating of the heart. In addition, irregularly shaped holes may result if the surgeon does not urge the optical fiber into the tissue at a constant rate. For example, a cavity within the new hole may be formed if the surgeon slowed down or paused briefly at a particular location because more tissue at that location would be ablated by the increase in laser energy emitted over time. In addition, the increase in emitted laser energy may cause excessive trauma to the surrounding tissue at that location

In many surgical applications, it may be desired to drill as large a hole as possible. For example, in treating ischemic myocardium, holes with larger diameters have larger inner surface areas; accordingly, more blood is able to perfuse into the ischemic tissue. The difficulty in drilling relatively large holes (for example, about 1 mm) with laser ablation is that the area of the lasing plenum increases exponentially with an increase in the diameter of the hole (the losing plenum being defined as the "bottom" of the hole subject to emitted laser energy). For example, the ratio between the areas of the lasing plenum of a hole with a 0.5-mm diameter and a hole with a 1-mm diameter is four. Conventional practice has been to increase the diameter of the optical fiber and, accordingly, the diameter of the laser beam to form larger holes. The power of the laser may also be increased. However, increasing the diameter of the laser beam results in an increase in the amount of energy emitted and, accordingly, an increase in the trauma of the surrounding tissue. In addition, the power of the laser energy can only be increased to a certain point until the capacity of the optical fiber is exceeded.

Accordingly, in view of the foregoing, it is an object of the present invention to provide methods and associated apparatus for delivering medicaments to tissue in a consistent and controlled manner. It is another object of the present invention to provide surgical apparatus for forming either complete or partial holes in tissue and then delivering medicaments to the holes and/or to surrounding myocardium tissue.

It is a further object of the invention to provide surgical apparatus and methods for promoting angiogenesis and endothelial growth in the myocardium. It is yet another object of the present invention to provide methods and associated apparatus for delivering medicaments to the myocardium while performing transmyocardial revascularization. SUMMARY OF THE INVENTION

These and other objects are achieved by the surgical apparatus and associated methods of the present invention which provides a medicament deliveiy system which forms holes or channels in tissue by removing tissue and then delivers medicament to the hole or channel or to the tissue surrounding the hole or channel. Tissue is preferably removed with laser ablation but may be removed by other methods, for example, with high-frequency electrical energy.

The system for delivering medicament to tissue in accordance with the present invention may be utilized to form a hole or channel in tissue, for example, cardiac tissue (myocardium), and then to deliver medicament, for example, a therapeutic agent for the treatment of cardiovascular disease, a growth factor that promotes angiogenesis, a gene that encodes for said growth factor, or any other therapeutic agent or gene therapy agent that promotes angiogenesis, to the tissue by partially or fully filling the hole or channel with the medicament, or by injecting the tissue surrounding the hole or channel with the medicament. This process may be repeated a plurality of time to form and fill a plurality of holes and channels in a targeted area of tissue. In contrast to conventional systemic deliveiy approaches, the medicament-deli very system of the present invention delivers medicament in a controlled manner to specific targeted tissue.

The medicament-delivery system of the invention may form channels in targeted tissue by removing tissue with laser ablation. It has been found that tissue ablation with laser energy stimulates a natural biological process of angiogenesis in the heart. In addition, administering medicaments such as growth factors that promote angiogenesis have been found to promote angiogenesis in the heart. Accordingly, a synergistic stimulation and promotion of angiogenesis in the heart is created by augmenting the heart's natural angiogenic response to laser ablation with the deliveiy of growth factor to those areas of the myocardium which have been ablated. The coupling of the heart's natural response to the formation of channels with the deliveiy of growth factor into or adjacent to those channels provides a benefit to patients not heretofore possible.

In a broad aspect of the present invention, a system for delivering medicaments to tissue includes an ablating and injecting device and a handpiece. The ablating and injecting device includes an optical fiber and a deliveiy member formed together into a unitary structure with cladding. The optical fiber has an inlet for receiving laser energy from a laser energy source and an outlet for emitting laser energy. The deliveiy member has a lumen with an inlet for receiving medicament from a medicament source and an outlet for injecting medicament. The handpiece is adapted to receive the ablating and injecting device in a controlled and movable relationship. In use, a distal end of the handpiece is placed against the target tissue The ablating and injecting device is advanced beyond the distal end of the handpiece and into the tissue while emitting laser energy fi om the optical fibei The emitted lasei energy ablates the tissue as the optical fiber advances The ablating and injecting device is then retracted from the tissue, thereby resulting in a channel formed in the tissue While the device retracts, medicament is injected from the delivery member into the channel, thereby providing a plug within the channel The medicament may include growth factor alone oi in combination with a cellular matnx which enhances angiogenesis in the tissue

Other aspects, features, and advantages of the piesent invention will become apparent to those peisons having oidinaiy skill in the ail to which the piesent invention pertains fi om the following description taken in conjunction with the accompanying diawings

BRIEF DESCRIPTION OF TH E DRAWINGS

FIG 1 is a pei spective view of an exemplaiy embodiment of a tissue dull of the present invention, FIG 1 A is a ci oss-sectional view of an exemplaiy optical fibei of the invention taken along line 1A of FIG 1 ,

FIG 2 A is a diagrammatic view of the exemplaiy tissue dull of the present invention, illustrating a handpiece receiving an optical fibei in a retracted position,

FIG 2B is a diagi ammatic view similai to that of FIG 2A, illustrating the optical fiber m an advanced position,

FIG 3 A is a diagrammatic view of an exemplaiy handpiece of the tissue dull of the piesent invention, lllusti ating the handpiece disassembled,

FIG 3B is a diagiammatic view similar to that of FIG 3A, illustrating the handpiece assembled, FIG 4 is a schematic view of an exemplaiy optical fibei of the present invention, particularly illustrating an eccentnc configui ation of an outlet portion of the optical fiber,

FIG 5 is a schematic view of an end sui face of the optical fiber illustrated in FIG 4,

FIG 6 is a schematic view of anothei exemplaiy optical fibei of the piesent invention,

FIG 7 is a schematic view of an end sui face of the optical fiber illustrated in FIG 6, FIG 8 is a diagrammatic view of an exemplary end surface of an optical fiber of the present invention, particulaily illustrating a l elationship between emitted laser eneigy and position of the end surface

FIG 9 is a schematic view of an exemplary source of laser energy of the present invention,

FIG 10A is a schematic view of an exemplaiy tissue drill of the pi esent invention, particularly illustrating a step of a prefeiied tissue-dulling pioceduie implementing the tissue drill,

FIG 1 OB is a view similar to that of TIG 10A, lllusti atmg a subsequent step in the tissue-drilling proceduie,

FIG I OC is a view similar to that of FIG I OB illustrating another subsequent step in the tissue-drilling procedui e,

FIG 10D is a view similar to that of FIG I OC, lllustiatmg yet another subsequent step in the tissue-drilling procedure, FIG 1 1 is a schematic view of tissue in which a hole has been dulled according to an exemplary method of the invention

FIG 12 is a schematic view of tissue m which a hole has been dulled accoi ding to another exemplary method of the invention

FIG 13 is a pei spective view of an exemplaiy medicament deliveiy system configured m accordance with the piesent invention,

FIG 14 is a schematic cross-sectional view of an exemplaiy ablating and injecting device for use in the medicament delivei y system of the pi esent invention

FIG 15 is a schematic view of an end sui face of the ablating and injecting lllusti aled m FIG 14, FIG 16 is a schematic view of an exemplaiy souice of lasei energy and medicament foi use in the medicament delivery system of the pi esent invention,

FIG 17A is a schematic view of an exemplary medicament deliveiy system of the present invention, particulai ly illustrating a step of a pi efei i ed ιnedιcaιnent-dehveι\ procedure of the invention, FIG 17B is a view similai to that of TIG 17A lllusti atmg a subsequent step the medicament-delivery pi ocedure, FIG 18 is a perspective view of a tissue-i emoval and medicament-delivery system in accordance with the invention, particulaily lllusti atmg a coupling assembly of the invention,

FIG 19 is a cross-sectional view of an exemplaiy coupling assembly taken along line 19 — 19 of FIG 18, with medicament injection and supply units shown schematically, FIG 20 is a diagrammatic view of an alternative embodiment of an exemplary ablating and injecting device for use in the medicament deliveiy system of the piesent invention,

FIG 21 is a diagrammatic view of anothei embodiment of an exemplaiy ablating and injecting device for use in the medicament deliveiy system of the present invention,

FIG 22 is a cross-sectional view of a tissue-removal and medicament-delivery device of the present invention, particulai ly configuied to l emove tissue with high-frequency electi ical energy,

FIG 23 is a ci oss-sectional view of an alternative embodiment of a tissue-i emoval and medicament-delivery device of the present invention

FIG 24 is a schematic view of a step of a tissue-i emoving pioceduie incorporating the device of FIG 22 oi 23, particulaily removing tissue with high-frequency electrical energy according to the invention,

FIG 25 is a schematic view of a medicament-delivery step of the invention, particularly illustrating the delivery of medicament to tissue sui i oundmg a hole oi channel formed in tissue,

FIG 26 is a cross-sectional view of anothei embodiment of an electπcal-eneigy tissue- removal and medicament-delivery device in accoi dance with the invention,

FIG 27 is a schematic view of anothei embodiment of a medicament-deliver,' system of the invention, particulai ly lllusti atmg an ablating and injecting device i eceived within a cathetei with rifling,

FIG 28 is a cross-sectional view of the medicament-delivery system of FIG 27, FIG 29 is a developmental view of an exemplaiy catheter with rifling foi use in the medicament-delivery system of FIG 27,

FIG 30 is a schematic view of an exemplaiy medicament delivery system of the present invention, illustrating needles around the penmetei of the head portion of the handpiece,

FIG 31 is a schematic view of the end sui face of the head portion of FIG 30, FIG 32 is a schematic view of the embodiment of FIG 30, particulai ly lllusti atmg a step of a preferred medicament-delivery pi ocedui e of the invention, FIG 33 is a schematic view of anothei exemplaiy embodiment of the head portion of the handpiece, illustrating nozzles around the perimeter of the head portion of the handpiece,

FIG 34 is an end view of yet anothei exemplaiy embodiment of the head portion of the handpiece, illustrating ports ai ound the penmetei of the head portion of the handpiece, FIG 35 is a perspective view of an alternative embodiment of a tissue-removal and medicament-delivery device of the piesent invention utilizing a single delivery lumen,

FIG 36 is a schematic cross-sectional view of the embodiment of FIG 35,

FIG 37 is a perspective view of yet anothei embodiment of a tissue-removal and medicament-delivery device of the present invention utilizing a single delivery lumen FIG 38 is a schematic cross-sectional view of yet another embodiment of of the device of the present invention utilizing at least one vacuum lumen and at least one deliver lumen

FIG 39 a schematic cross-sectional view oi a step of an alternate exemplary embodiment of an electiical-energy tissue-i emoval and medicament-delivery device of the present invention, and FIG 40 is a schematic ci oss-sectional view of the embodiment of FIG 39, particularly illustrating a step of a prefeii ed medicaiuent-deliveiy procedure of the invention

DETAI LED DESCRI P 1 1ON OF EXEM PLARY EM BODIM ENTS

Referring to the di awings in moi e detail, in TIG 1 an exemplary embodiment of a tissue dull 50 of the present invention is illusti ated in conjunction with a souice of laser eneigy 52 Exemplary tissue drill 50 foi ms holes or channels in tissue by lasei ablation in a consistent, controllable, and programmable manner The fu st portion of the following descuption focuses on the principles of tissue ablation and the foi ming of channels m tissue These principles of the present invention ai e then l eadily applied to a system foi delivenng medicaments to the tissue in which the channels are formed, which will be discussed in more detail below

Ablation is the piocess of fi agmentmg long molecules into short gaseous molecules Much of the tissue in living organisms, including the human body, is made up mostly of watei (e g , about 75%) with organic material making up the i emaining portion The molecules of organic material consist of atoms of caibon nitrogen oxygen and hydrogen that are attached together through covalent bonds Ablation is the pi ocess of bi eakmg these covalent bonds

Tissue dull 50 utilizes the ablation pi ocess to bi eak molecules of tissue apart, thereby forming holes or channels in the tissue The ablation pi ocess will be discuss in moi e detail below Exemplary tissue dull 50 includes a handpiece 54 foi manipulation by a user and an optical fiber 56, which is shown in FIG 1 A, for ti ansmittmg laser eneigy fi om laser eneigy source 52 Optical fiber 56 has an outlet portion 58 foi emitting laser energy Outlet portion 58 functions substantially as a dull bit In operation, outlet portion 58 is moved fiom a reti acted position (which is shown in the solid line) to an advanced position (which is shown by the phantom line) while emitting laser energy Aπow A i epi esents outlet portion 58 moving to the advanced portion, and airow L represents lasei eneigy emitted from outlet portion 58 1 issue is ablated by laser energy as outlet portion 58 is advanced, thereby foi ming a hole or a channel in the tissue Exemplary tissue drill 50 may also lotate outlet portion 58 while moving to the advanced position, which is iepiesented by arrow R Aftei reaching the advanced position, outlet portion 58 may be withdi awn to the l eti acted position which is iepiesented bv aπ ow B The advancing and retracting of outlet portion 58 is pi efei ably along a central axis of optical fiber 56 Any rotation of outlet portion 58 is piefei ably about the centi al axis of optical fibei 56 The axial and rotational movement of outlet portion 58 will be discussed in moi e detail below

Exemplaiy outlet portion 58 of optical fibei 56 has an end sui face 60 with an outlet 62 from which laser eneigy is emitted Outlet 62 is piefeiably offset fiom or eccentiic to the central axis of outlet portion 58 so that as outlet portion 58 tates outlet 62 i otates about the central axis Accordingly, lasei eneigy emitted fi om outlet 62 as outlet portion 58 iotates is not focused at a single point but is rathei disti ibuted about the central axis Alternatively speaking the eccentric relationship of outlet 62 with l espect to the central axis of outlet portion 58 preferably produces a gradient of lasei eneigy as outlet portion 58 axially advances, with the highest level of laser energy at the central axis, which energy deci eases toward a peupheial edge The eccentricity of outlet portion 58 will also be discussed in more detail below Handpiece 54 may be implemented accoi dmg to a variety of configuiations Toi example, handpiece 54 may be a flexible cathetei utilized in endovasculai procedui es and having a plurality of lumens to facilitate visualization, flushing and aspn ation In this l egai ci outlet portion 58 may advance beyond a distal end of the cathetei to vascularize tissue, such as on the inside the left ventricle of the heart

handpiece 54 may be formed as a tiocai sheath and positioned intercostally (l e , between the ubs) foi tissue access Handpiece 54 ma\ also be formed in a gooseneck-like configuiation with a pluiality of articulated joints which m^ be bent to assume and retain a paiticulai shape Moieovei handpiece 54 may be a conduit with flexible cable sheathing Accoidingly, in a genei l sense, handpiece 54 provides a "user interface" for delivering outlet portion 58 to a tai get site, which may be accomplished either by direct physical manipulation by a surgeon or by pi ogi mmed mechanical control

An exemplary handpiece of the pi esent invention is illustrated in FIGS 2A and 2B Exemplary handpiece 54 may include a body portion 64 and a coupling portion 66 Exemplary body portion 64 has a distal end 68 Exemplai y coupling portion 66 is adapted or configuied to receive optical fiber 56 in a conti oiled and axially movable relationship so that outlet portion 58 may be advanced beyond distal end 68 of body portion 64 In addition, coupling portion 66 may be adapted to receive optical fiber 56 in a l otatable relationship so that at least outlet portion 58 of optical fiber 56 may l otate If handpiece 54 is configured as a catheter or similai flexible tubular member, the inner sui face of the tubulai member serves as a coupling portion by receiving optical fibei 56 in a conti oiled, axially movable, and/or l otatable l elationship

The retracted position of outlet portion 58 as shown in FIG 2 A may be defined as a position in which end sui face 60 is positioned substantially at oi neai distal end 68 of body portion 64 Accordingly, end sui face 60 may pioject slightly beyond distal end 68 or, alternatively, may be eithei pioximal to oi substantially aligned (oi coplanar) with distal end 68 The advanced position of outlet portion 58 as shown in FIG 2B may be defined as a position in which end surface 60 with outlet 62 projects a distance d beyond distal end 68 of body portion 64 As will be discussed in moi e detail below, distance a\ which end sui face 60 pi ojects beyond distal end 68 is prefei ably pi edetermmed, adjustable, and/oi pi ogi ammable

With additional reference to FIGS 3 A and 3B, exemplary coupling portion 66 may include a drive which is comprised of a tubulai member 70 and a collai 72 Tubular membei 72 receives optical fiber 56 and may have a chuck 74 foi letain g optical fiber 56 theieto Tubulai member 72 may also have annulai thi eadmg 76 toi med along a length theieof Collai 72 is disposed within body portion 64 and has complementaiy innei thi eadmg 78 Exemplaiy tubular member 72 is s dably and l otatably l eceivable withm body portion 64 with annulai thi eadmg 76 engaging with inner threading 78 of collai 72, as shown in FIG 3B Accoi dingly, rotation of tubular member 70 causes tubular member 70 to move axially As optical fiber 56 is retained by chuck 74, optical fiber 56 with outlet portion 58 moves axially with tubular member 70 In an alternative embodiment of handpiece 54 such as a catheter, l ather than disposing coupling portion 66 and a duve on handpiece 54, these elements may be provided at a pioximal location such as at laser apparatus 52 In this i egai d cathetei -configui ed handpiece 54 ietams optical fiber 56 within a body portion which prevents buckling and which dehvei s outlet portion 58 to a target site but which is substantially fi ee of coupling and dnve apparatus

Referencing FIG 4, in addition to outlet portion 58, exemplaiy optical fiber 56 has an elongate portion 80 A coi e 82 and a cladding 84 define optical fibei 56 and extend along elongate portion 80 and outlet portion 58 Core 82 has an inlet 86 for receiving lasei energy and outlet 62 (see also FIG 1 ) foi emitting lasei eneigy Core 82 and cladding 84 may be made of high-purity silica glass oi sapphn e, with coi e 82 having a highei index of refraction than that of cladding 84 so that modulated pulses of laser eneigy move along core 82 without penetrating cladding 84 Although optical fiber 56 may be configured according to any dimensions, for many applications a length of elongate portion 80 may range from about 0 5 metei (m) to more than 2 m to provide a surgeon with sufficient maneuverability, and a length lu of outlet portion 58 may range up to about 50 millimetei s (mm) so that holes of different lengths may be formed in tissue Foi applications othei than medical, optical fibei 56 may be dimensioned accordingly to accomplish the particular application Core 82 of optical fibei 56 has an axis E along elongate portion 80 and an axis O at outlet 62 With additional iefei ence to FIG 5, core 82 along outlet portion 58 angles away from and is oblique to core 82 along elongate portion 80 At end suiface 60, axis O of coie 82 at outlet 62 is offset fi om or eccenti ic to axis E of coi e 82 of elongate portion 80 by a distance δ Accordingly, lasei eneigy emitted fi om outlet 62 is disti ibuted about axis E as optical fibei 56 rotates about axis of i otation E Fuithei , the disti ibution of lasei eneigy is across the entire surface area of end suiface 60 as optical fibei 56 make one complete revolution At end surface 60, outlet 62 may be configured so that axis O of coi e 82 is eithei oblique to axis E oi, as shown, parallel to axis E

An alternative exemplary embodiment of optical fiber 56 is illustrated in FIGS 6 and 7 In addition to core 82 and cladding 84, exemplaiy optical fiber 56 may include auxiliary cladding 88 disposed about outlet portion 58 Similai to the embodiment shown in FIG 4, to offset axis O of outlet 62 from axis of rotation E by distance δ, coi e 82 of outlet portion 58 is oblique to core 82 of elongate portion 80 Auxiliary cladding 88 compensates for the oblique relationship of core 82 (and cladding 84) of outlet portion 58 with lespect to core 82 (and cladding 84) of elongate portion 80 Auxiliary cladding 88 accoi dingly pi ovides a pieferred cylinducal configuration of outlet portion 58 so that outlet portion 58 iotates about axis E as elongate portion 80 rotates about axis E Fuithei, in addition to axis O at outlet 62 being eccenti ic to

- n axis E, axis O of core 82 may be oblique to axis E at outlet 62, l athei than a pai allel relationship as shown in FIG 4

As illustrated in FIGS 6 and 7, end sui face 60 (including outlet 62) is substantially perpendicular to axis E of exemplary optical fibei 56 To foi m the perpendicular l elationship, core 82 and cladding 84 are ground or polished at an angle oblique to axis O, theieby removing portions of core 82 and cladding 84 shown by phantom line P Accordingly, exemplaiy end surface 60 is substantially planar Alternatively end sui face 60 may be convex, concave, or other configuration depending upon a paiticulai implementation of outlet portion 58

With particular reference to FIG 7, end sui face 60 of exemplary optical fiber 56 has a circumference Ces defined along an outer edge 90, and outlet 62 of core 82 has a circumference Co defined along outei edge 92 Circumfei ence Ct, and cii cumference CC) are coextensive along an arc length α of outer edges 90 and 92 This l elationship allows laser eneigy to be emitted from outlet 62 at outei edge 90 of end surface 60 As outlet portion 58 i otates, lasei energy is emitted along circumfeience C.b of rotating end sui face 60 Aie length α may range fi om a single tangent point to several seconds, minutes, or degi ees as desired

Diameter d0 of outlet 62 is piefeiably gieatei than about one half of diameter dts of end surface 60 Accordingly, outlet 62 has a surface area which is at least one quaitei of that of end surface 60 This relationship in surface ai ea allows lasei energy to be emitted from a substantial percentage of end surface 60 Fui thei, lasei eneigy is not emitted fi om the entn e end sui face 60 simultaneously but rather ovei the time it takes outlet portion 58 to make one I evolution about axis E An exemplaiy commei cial embodiment of optical fiber 56 for use in tiansmyocardial revasculaπzation entails a diametei dus of end sui face 60 (and outlet portion 58 of approximately 1 mm and a diametei d0 of outlet 62 of appi oximately 0 6 mm Generally speaking, the dimensions of outlet portion 58 ai e detei mined by the type of procedure being performed and the desired size of the hole, with diametei d„ of outlet 62 being at least one half of diameter dtb of end surface 60 For example, if a hole with a 1 5-mnι diametei is desn ed, then diameter dLb ol end surface 60 (and outlet portion 58) should be about 1 5 mm diameter d„ of outlet 62 ma\ accordingly lange from about 0 75 mm to slightly less than 1 5 mm, but is pi eferably about 0 8 mm For many medical applications, it is contemplated that diametei dt of end surface 60 ma\ range from about 0 2 mm to more than 2 5 mm, with diameter d„ of outlet 62 l ang g fi om less than about 0 1 mm to about 2 mm or moi e Foi specific medical applications such as transmyocardial revasculaπzation (which will be discussed below), diameter dLS of end suiface 60 may range from about 0.6 mm to about 2 mm, with diameter d„ of outlet 62 ranging from about 0.3 mm to about 1 mm.

With additional reference to FIG. 8, end surface 60 is schematically illustrated during rotation, with outlet 62 shown at progressive instances in time //, t2, , and t4 while rotating about axis E. Because of the relationship between the surface areas of end surface 60 and outlet 62, laser energy is continuously emitted from an area 94 of end surface 60. In other words, area 94 represents an intersection of the positions of outlet 62 at every instance of time while rotating about axis E. Laser energy is accordingly emitted at intervals at other areas of end surface 60 depending upon the position of outlet 62 at a particular instance in time. The relationship between laser energy emitted from exemplary end surface 60 per revolution of outlet 62 about axis E with respect to distance from axis E is illustrated graphically in FIG. 8. Emitted laser energy per revolution of outlet portion 58 decreases from a constant level at area 94 to a lower level at outer edge 90 of end surface 60. In the graph, outer edge 90 is a distance from axis E substantially equal to radius r of end surface 60. Depending upon a particular configuration of exemplaiy end surface 60 and outlet 62, the decrease in laser energy or flux with respect to position may be a linear function as shown or a nonlinear function. Also, the relative level of energy per revolution at area 94 and at radius r^ is illustrative only, as the level of energy at the periphery of end surface 60 may vary according to the particular surgical procedure. For example, the energy flux at radius rL.„ may be at a relatively low level when compared to the constant level at area 94.

In accordance with this energy distribution per revolution of the present invention, while ablating tissue to form a hole, the transference of laser energy to peripheral or surrounding tissue is less than at a center of the hole being formed. This distribution of laser energy may limit trauma to tissue in which holes or channels are formed. More specifically, as outlet portion 58 moves through tissue while rotating and emitting laser energy, outer edge 90 of end surface 60 is adjacent to and contacts the surrounding tissue which defines the hole being formed. As the level of emitted laser energy at outer edge 90 is lower than that centered about axis E (which essentially defines the center of the hole being formed), damage to the surrounding tissue is reduced, resulting in less trauma to the tissue It is believed that tissue with a relatively low level of trauma has a likelihood to experience angiogenesis, or the formation of new blood vessels in the tissue. This reduced-trauma feature of the present invention will be discussed in more detail below. An exemplaiy process to form an eccentric outlet portion 58 as described above involves placing the distal end of optical fiber 56 within a Teflon'1" tube at an angle, with cladding 84 contacting the inner surface of the tube at one point. The tube may then be filled with epoxy which surrounds the distal end of optical fiber 56 except at the point at which cladding 84 contacts the tube. After the epoxy has cured and hardened, the tube is removed, and the distal surface of the epoxy and optical fiber 56 is polished to define end surface 60 at the point where cladding 84 defines an annular edge of outlet portion 58. End surface 60 may also be formed with a lens to control the emission of the laser energy in a particular manner. An inner diameter of the tube for forming outlet portion 58 essentially determines the diameter of outlet portion 58 (i.e., diameter d s of end surface 60). According to this process, optical fibers 56 having outlet portions 58 of different diameters may be formed, enabling surgeons to form holes with a variety of diameters. In addition, a plurality of outlet portions 58 each having a different diameter may be formed, each of which being able to be coupled to an optical fiber, so that a set of interchangeable "drill bits" is at a surgeons disposal during a particular procedure Optical fiber 56 may be reusable or disposable, as may outlet portion 58 and handpiece 54.

With further reference to FIGS. 1 and 3 A, exemplary of handpiece 54 may include a head portion 96 connectable to a distal end of body portion 64 by a neck 98. Distal end 68 of body portion 64 is accordingly defined by a tissue end 100 of head portion 96. Exemplary head portion 96 may be conical so that tissue end 100 has a larger diameter than body portion 64. Tissue end 100 provides a working surface or a tissue-engaging surface for positioning handpiece 54 over and against a surgical site in which a channel is to be drilled into tissue Exemplary head portion 96 may also have an aperture 102 formed therein. Aperture 102 may function as a window for viewing a surgical site when tissue end 100 is placed against tissue. Aperture 102 may also function as a vent for exhausting gases which may be generated by laser energy ablating tissue. As shown in FIG. 1 , exemplaiy neck 98 may be angular to enhance the positioning of head portion 96 against tissue. In this regard, neck 98 may be configured as a gooseneck with articulable joints for assuming and retaining a desired shape. Exemplary head portion 96 and neck 98 are preferably tubular, thereby providing an inner continuum with body portion 64 in which optical fiber 56 is receivable In particular procedures, it may be preferable to know where a hole has been drilled in tissue. However, the nature of the tissue or the size of the hole may render it difficult for the surgeon to determine where a hole has already been formed. Accordingly, the newly formed hole drilled in tissue may be marked In this regard, head portion 96 may include apparatus for marking where a hole has been drilled in tissue For example, tissue end 100 may have an inking device which dispenses biocompatible ink or dye on the tissue where a hole has been formed The ink may be applied to the tissue through direct contact with tissue end 100 or, for example, by spraying. Exemplary handpiece 54 may have a reservoir for storing and dispensing a colored liquid or a paniculate solid to the tissue Fluorescent material may be used to enhance visualization. Other indicia may be applied to the tissue by handpiece 54 or head portion 96 at the target site; for example, alphanumeric indicia may indicate the parameters of the laser energy emitted from outlet 62 to form a particular hole With further reference to FIGS. 2A to 3B, exemplaiy coupling portion 66 may include a spring 104 receivable against a seat 106 formed on a distal end of collar 72, and a stop 108 disposed on a distal portion of tubular member 70 Spring 104 and stop 108 define a mechanism for controlling a position of tubular member 70 within body portion 64, and may be configured to facilitate the advancement and retraction of tubular member 70 Exemplaiy source of laser energy 52 is illustrated in FIG 9 Laser energy source 52 includes a laser 1 10 for generating laser energy L Exemplary laser energy source 52 may include a drive assembly 1 12 for operatively associating with handpiece 54 and optical fiber 56, and may also include a control unit 1 14 with a user interface 1 16 Exemplary drive assembly 1 12 may include a coupler 1 18 for connecting with optical fiber 56, optics 120 for modifying laser energy L as desired, and a drive/motor 122 Exemplary coupler 1 18 is associated with optics 120 for transferring laser energy L from laser 1 10 to the inlet of optical fiber 56 Exemplaiy coupler 1 18 is also associated with drive/motor 120 for rotating optical fiber 56

As discussed above in reference to FIGS 2A and 2B, exemplary coupling portion 66 of handpiece 54 translates rotational movement of optical fiber 56 to axial movement to advance and to retract outlet portion 58 Exemplary drive assembly 1 12 preferably rotates optical fiber 56. For example, coupler 1 18 may secure and retain a proximal end of optical fiber 56, with motor/drive 122 rotating coupler 1 18 which also rotates optical fiber 56. Drive assembly 1 12 may rotate optical fiber 56 in a first direction, for example, as shown by arrow Rj in FIG. 2A, to cause optical fiber 56 to advance axially as shown by arrow A When outlet portion 58 reaches the desired advanced position, drive assembly 1 12 may then rotate optical fiber 56 in an opposite second direction, as shown by arrow R2 is FIG 2B, to cause optical fiber 56 to retract axially as shown by arrow B Exemplary drive assembly 1 12 may oscillate optical fiber 56 (that is, rotate optical fiber 56 clockwise and countei clockwise as shown by ai rows Rj and R2) so that outlet portion 58 recipi ocates between the l eti acted position and the advance position

Exemplaiy laser energy soui ce 52 prefei bly conti ols w hen lasei energy L is emitted from outlet portion 58 of optical fiber 56 For example, conti ol unit 1 14 in association with laser 1 10 and drive assembly 1 12 may limit the emission of laser energy L to only when outlet portion 58 moves to the advance position Lasei energy L may then be terminated during the retraction of outlet portion 58 Alternatively, if duve assembly 1 12 is reciprocating outlet portion 58, laser energy L may be transmitted

din ing the advancing stroke of outlet portion 58, the emission of laser energy L may then be tenninated at the end of the advancing stioke The teimination of laser energy L upon i eachmg the advanced position is pi eferably automatic and conti oiled by lasei eneigy soui ce 52 Alternatively, laser eneigy L may be tenninated by a device such as a pressure sensoi which detei mines when the distal end of outlet portion 58 advanced completely through a section of tissue, e g , the wall of the heart This contiol of laser energy L is preferable during pai ticulai applications of tissue drill 50, which will be discussed in more detail below

With fui thei iefei ence to FIG 1 A optical fibei 5e> is pi efei ably leceived within a housing 124 In addition to piotectmg optical fibei 56, exemplaiy housing 124 constiams an> torsional flexing or bending of optical fibei 56 which may lesult fi om the lotation by duve assembly 1 12 Exemplary optical fibei 56 may include a complementary coupler 126 foi connecting with couplei 1 18 of lasei eneigy soui ce 52 Complementary coupler 126 pi efei ably provides a releasable association with couplei 1 18 so that other optical fibers in accoi dance with the present invention may be connected to lasei eneigy soui ce 52 Exemplaiy housing 124 preferably extends between couplei 126 and chuck 74 of coupling portion 66 to piovide mtegi al protection of optical fibei 56 between lasei enei y soui ce 52 and handpiece 54 Exemplary lasei eneigy soui ce 52 may control a numbei of pai ameters of tissue dull 50 including distance c/ at which outlet portion 56 advances, a speed at which outlet portion 56 advances, and a level at which lasei energy is emitted fi om outlet 62 Control unit 1 14 in association with user interface 1 16 pieferably conti ols, pi ograms, monitoi s, and/or adjusts each of these parameters depending upon a pai ticulai tissue-dulling application Foi example one the many applications of tissue dull 50 is foi dulling holes oi channels into or thi ough heart walls This procedure is known as ti ansiii) υcai ial i

ciscii/ai izalion oi , moi e simply, as TMR FIGS 10A through 10D schematically illusti ate an exemplary TM R procedure implementing tissue dull 50 of the present invention

A heart wall 1 30 is illusti ated m FIG 10 and includes myocai dium, oi heart muscle, 132 positioned between an outei sei ous layei oi epicai dium 134 and an innei membrane or endocardium 136 It has been found to be medically beneficial to revasculauze the myocai dium of patients suffering from severe ischemic cai diomyopathy The revasculaπzation of the myocardium 132 involves forming new channels in the tissue By implementing exemplary tissue drill 50 of the pi esent invention, new channel may be formed in the myocardium in a controlled, consistent, and progi ammable mannei Pi IOI to a TMR pi ocedui e, the level at which lasei 1 10 is to genei ate lasei energy 1 and the frequency at which lasei energy L is to be pulsed

be detei mined In addition, distance d at which outlet portion 58 is to advance beyond distal end 68 and the speed at which outlet portion 58 is to rotate may be detei mined These pai ametei s may be stored in conti ol unit 1 14 and varied or programmed via usei interface 1 16 Din ing the TMR pi ocedui e, access to the patient's chest cavity is pi ovided, pi eferably by a minimally invasive pi ocedui e such as an intei costal incision using trocai sheaths Access to the patient's heart is then provided, foi example, by incising the peucai dium With outlet portion 58 in the retracted position, a sui geon may then maneuver head portion 96 of handpiece 54 into the chest cavity and position tissue sui face 100 against the epicai dium 134, as shown in FIG 10A As discussed above, outlet portion 58 may pi oject slightly beyond distal end 68 (that is, tissue end 100) when in the i eti acted position to pi ovide the surgeon with a tactile feel of the position of end surface 60 on the epicardiiim 134

When in the desired position on the epicai dium 1 34 tissue dull 50 may be activated This activation may be accomplished manually by an assistant via usei intei face 1 16 oi by the surgeon with a foot or a hand tuggei Alternatively, activation of tissue dull 50 may be synchronized with the electi ical activity of the heart thi ough the use of an electrocai diogiam (EKG) machine Activation of tissue drill 50 causes laser enei gy soui ce 52 to generate and transmit laser energy to optical fibei 56 Activation also causes optical fibei 56 to i otate and advance outlet portion 58 thi ough the epicai dium 134 and into the myocai dium 1 32 of the heart wall 130, as shown in FIG 10B

Outlet portion 58 continues to advance thi ough the myocai dium 132 and thi ough the endocardium 136 When end sui face 60 of outlet portion 58 has advanced through the endocardium 136 and is positioned within the left ventricle of the patient's heart as shown in FIG. I OC, the emission of laser energy is preferably terminated, and the outlet portion 58 is retracted. A new channel 138 through the heart wall 1 0 results from this procedure as shown in FIG. 10D. Oxygenated blood from the left ventricle may enter the new channel 1 38 through the endocardium 136 and perfuse the tissue of the myocardium 132 surrounding the new channel 138. When handpiece 54 is configured as a catheter, outlet portion 58 advances through the endocardium 136 and then into the myocardium 132 Because outlet portion 58 may be programmed to advance a predetermined distance, outlet portion 58 may either continue to advance completely through the epicardiiim 1 4 or begin to retract the predetermined distance within the myocardium 132, thereby forming a hole in the heart wall 130 rather than a channel through the heart wall 1 30

As mentioned above, reduced trauma to the myocardium 1 34 surrounding the new channel 138 results from the eccentric relationship between outlet 62 and rotational axis E This reduced trauma may enable the surrounding tissue to regenerate vascular tissue from the new channel 138 and into the myocardium 134 or to experience angiogenesis In addition to the eccentricity of outlet portion 58, the level of trauma inflicted on the surrounding tissue is mediated by the level of laser energy emitted from outlet 62, which will now be discussed With reference to FIG 9, the energy level at which laser energy L is generated and transmitted to optical fiber 56 may be varied, programmed, and controlled according to each tissue-drilling application. For example, tissue drill 50 may be configured for drilling holes in all types of animal tissue and plant tissue, as well as other substances The parameters which define the characteristics of laser ablation include frequency, energy per channel, pulse width, and pulse rate. As mentioned earlier, ablation is a process of breaking bonds between atoms in molecules by adding energy to the molecules One preferred level of the laser energy L for TMR applications is to limit the energy per pulse to less than about 100 milliJoules per square millimeter of area (mJ/mm"). More preferably, an energy per pulse of about 30 mJ/mm2 has been found to ablate cardiac tissue at a substantially reduced level of trauma The energy per pulse of laser 1 10 may be varied according to specific tissue-drilling procedures

With further reference to FIGS. 3A and 3B, the drive may be configured to control the rate at which outlet portion 58 advances and retracts The rate of advancement is controlled by the speed at which optical fiber 56 rotates and the pitch of the complementaiy threading of collar 72 and tubular member 78. For smooth and continuous operation, it has been determined that optical fiber 56 and, accordingly, outlet portion 58 should rotate at a speed under about 5,000 revolutions per minute (RPM). For TMR applications of tissue drill 50, a rotational speed ranging from about 1,000 RPM to about 2,000 RPM is preferred. In this regard, a specific TMR configuration of tissue drill 50 may be as follows Optical fiber 56 may rotate at about 1 ,340 RPM The pitch of threading 76 and 78 may be configured so that outlet portion 58 advances at a rate of about 15.5 millimeters per second (mm/s). With a rotational speed of 1 ,340 RPM, it takes about 46 milliseconds (ms) for outlet portion 58 to complete one rotation. For TMR applications, laser 1 10 may emit pulses of laser energy L of about 20 nanoseconds (ns) in duration, with each pulse being separated by about 4 ms The pulse rate may be about 10 pulses per revolution (or at about every 36° of rotation) or about 240 pulses per second.

Rather than advancing and retracting outlet portion 58 at a constant rate as described above, tissue drill 50 may be configured such that outlet portion 58 moves at varying rates of speed between the retracted and advanced positions. The slower outlet portion 58 advances (or retracts) while emitting laser energy L, the more tissue that becomes ablated because the tissue is subject to more laser energy over time. Accordingly, a hole may be formed with a diameter greater than diameter cU of end surface 60 (and outlet portion 58) by advancing outlet portion 58 at a speed which allows laser energy L to ablate a greater amount of tissue Alternatively, the power of laser energy L may also be varied during the advancement of outlet portion 58 so that the tissue is subjected to more or less laser energy L. Generally speaking, a surgeon may program tissue drill 50 to ablate tissue at varying levels of energy per unit time to form holes of varying desired diameters or configurations The energy per unit time may be adjusted by varying either the speed at which outlet portion 58 advances (which varies the time the tissue is subject to laser energy) or the level of laser energy, or both.

In order to form the substantially cylindrical hole 138 shown in FIG 10D, tissue drill 50 advanced outlet portion 58 at a substantially constant speed, and laser energy source 52 emitted laser energy at a substantially constant level. However, if a conical-shaped hole 140 as shown in FIG. 1 1 is desired, with the apex of the hole 140 positioned at the epicardium 134 and the base of the hole 140 positioned at the endocardium 136, then tissue drill 50 may be configured to advance outlet portion 58 at a decreasing rate (i.e., moving at a slower and slower speed) while advancing through the heart wall 130 from the epicardium 134 to the endocardium 136. Accordingly, a greater amount of tissue is ablated as outlet portion 58 advances at a slower speed The resulting hole 140 has a diameter substantially equal to diameter d^ of outlet portion 58 at the epicardium 134 and a diameter larger than diameter d s at the endocardium 136. By forming the hole 140 with a relatively large diameter at the endocardium 136 improves the patency of the hole and, therefore, the perfusion of the blood into the myocardium 132. In addition, by forming a hole with as small a diameter as possible at the epicardium 134 minimizes bleeding and trauma. With reference to FIG. 12, another noncylindrically shaped hole 142 is shown. Rather than forming hole 142 by advancing outlet portion 58 fiom the epicardium 134 to the endocardium 136 as shown in FIG. 1 1 , hole 142 is formed endovascularly, with outlet portion 58 advancing from the endocardium 136 and into the myocardium 132 a predetermined distance d. As mentioned above, to form holes endovascularly, handpiece 54 may be configured as a catheter, with access to the left ventricle of the heart provided through, for example, a femoral artery and the aorta. To form hole 142 with a diameter greater than diameter d, of end surface 60 at the endocardium 1 6, tissue drill 50 is configured to advance outlet portion 58 relatively slowly at or near the epicardium 136 and then to increase the speed. This results in more tissue being ablated at or near the endocardium 136 than at the "bottom" of hole 142 within the myocardium 132. Laser energy may also be emitted while outlet portion 58 retracts to ablate more tissue toward the endocardium 136. The speed oϊ advancement may be varied by varying either the revolutions per second at which outlet portion 58 rotates or the pitch of threading 76 and/or 78, or both. As mentioned above, rather than varying the speed at which outlet portion 58 advances, the level of emitted laser energy L may be varied. In this regard, to form hole 142, tissue drill 50 may be configured to emit laser energy L at a relatively high level when outlet portion 58 begins to advance, and then to decrease the level as outlet portion 58 advances distance d.

Alternatively, rather than adjusting the speed or the energy level, outlet portion 58 may reciprocate a multiple of times either at increasing depths or at decreasing depths. For example, referencing FIG. 12, if the desired depth of the hole to be formed is distance </ (that is, the distance end surface 60 advances beyond the distal end of handpiece 54), then tissue drill 50 may be configured to advance outlet portion 58 a distance d on a first stroke and then to advance outlet portion 58 a distance which incrementally decreases for each subsequent stroke for a predetermined number of strokes. Accordingly, even though the speed at which outlet portion 58 advances and the level at which laser energy L is emitted, hole 1 2 may be formed with a relatively large diameter at the endocardium 136 and tapered toward the epicardium 134 because tissue toward the endocardium 134 is subject to repeated laser energy with the multiple strokes of outlet portion 58. Therefore, a greater portion of this tissue is ablated because of the increased level of energy received per unit time Alternatively, l athei than decreasing the distance of the sti oke, the distance of each multiple stioke may be incrementally increased to form hole 140 of FIG 1 1 In addition, if it is desired to form a hole with a relatively laige-diametei inner chambei , then tissue dull 50 may pause outlet portion 58 at a predetermined distance for a pi edetermined amount of time to concenti ate laser eneigy at one location to ablate a lelatively large portion of tissue at that location

Deliveiy of Medicament to Tissue

An exemplary system for delivering medicament to tissue which is configured in accoi dance with the present invention is illusti ated in FIG 13 Exemplaiy medicament delivery system is referenced with numeral 150 and may be utilized to foi m a hole or channel in tissue, foi example, cardiac tissue (myocaidium), and then to delivei medicament foi example, a thei apeutic agent foi the treatment of cardiovascular disease, oi a gi owth factoi to the tissue by partially oi fully filling the hole or channel with the medicament by injecting medicament into the tissue suu oundmg the hole or channel, or by admmistei mg medicament to a l egion which includes the hole oi channel and the suπ ounding tissue This pi ocess may be l epeated to foi m and fill a plui ality of holes and channels in a targeted ai ea of tissue In conti ast to conventional systemic deliver,' appi oaches, the system 150 of the present invention delivers medicament in a conti oiled mannei to specific taigeted tissue The terms hole and channel used heiem indicate any space foi med in tissue oi through a section of tissue which space may be substantially l egular m shape such as cii cular, elliptical curvilineai , or i ectilmear, oi substantially in egulai in shape 1 he exemplaiy embodiment of deliveiy s> stem 1 50 illusti ated in TIG 13 forms the holes oi channels by i emoving tissue with laser ablation As mentioned abov e, it has been found that tissue ablation with laser energy stimulates a natuial biological piocess of angiogenesis in the heart In addition, angiogenic-enhancing gi owth factoi have been found to pi omote angiogenesis in the heart Accordingly, a synergistic stimulation and pi omotion of angiogenesis in the heart is ci eated by augmenting the heart's natui al angiogenic i espouse to lasei ablation with the deliveiy of gi owlh factor to those areas of the myocai dium which have been ablated The coupling of the heart's natural response to the foi mation of channels with the delivery of angiogenic gi owth factor into oi adjacent to those channels pi ovides a benefit to patients not possible pnor to the pi esent invention

Medicament deliveiy system 1 50 may include many of the same elements as exemplaiy tissue drill 50 discussed above Elements of medicament deliveiy s> stem 150 which ai e substantially analogous to elements of tissue dull 50 use like l efei ence numei als with the addition of a pnme (') For example, medicament delivery system 150 includes a handpiece 54' which may be substantially

_ m _ the same as handpiece 54 of tissue dull 50 1 his lefeiencmg convention will be used in the descπption hereunder, and the eailier descuption of such analogous elements will not be repeated in connection with medicament delivery system 150

In cardiac applications of the system 1 50 of the invention, the administration of medicament such as endothelial growth factor to cardiac tissue such as myocaidium piomotes cardiovascular angiogenesis Growth factoi s aie proteins that stimulate oi enhance cell giowth Giowth-factor proteins may be packaged in caiuei molecules to specifically enhance angiogenesis For example, the naked DNA of the growth-factor piotein may be combined with a cellulai matux Examples of cellular matrixes include fibrin, plasma and any othei staictuie that enhances the biocompatibility oϊ the growth factor in the tissue the angiogenic activ ity of the giowth factoi, and/or the sustained release of the giowth factor into the tissue Theie ai e many commeicially available giowth factors that promote angiogenesis such as vascular endothelial giowth factoi (VEGr), basic fibroblast growth factor (bFGF), tiansfounmg giowth factoi -beta (TGF-β) and platelet-denved giowth factoi (PDGF) 1 he term medicament used herein may include giowth factor alone, giowth factor in combination with a cellulai matnx, oi giowth factoi in combination with any other component that is known to assist in the deliveiy of the giowth factoi In addition medicament could include any othei substance that stimulates angiogenic activity m the heart

To deliver medicament to myocai dium exemplar, medicament deliveiy system 150 includes a tissue-removal device foi foiming holes oi channels m tissue such as a source of lasei eneigy and medicament 152 and an ablating and injecting device 154 As discussed in more detail below, ablating and injecting device 154 includes an optical fibei which ieceives lasei eneigy fiom souice 152 for ablating tissue to foim a channel, and a deliv eiy membei which ieceives medicament fiom source 152 for injection into the channel In caidiac applications, system 150 is able to delivei growth factor dnectly into the ischemic myocai ium of a patient to pi omote the growth of endothelial cells

With additional refei ence to FIGS 14 and 1 5 exemplary ablating and injecting device I 54 may include an optical fiber 1 56 and a deliveiy membei 158 molded togethei into a unitary sti uctui e with cladding 160 As descnbed above, exemplaiy optical fibei 1 56 may include a coie 82 and a cladding 84', with coi e 82' having an inlet 86' foi l eceivmg lasei eneigy and outlet 62' for emitting laser energy, as indicated by anow L in FIG 13 Exemplai y delivery membei 1 8 mav include a wall 162 in which is defined a lumen 1 4 with an let 166 for l eceivmg medicament and an outlet 168 for piovidmg medicament, which is indicated by anow M in FIG 13 Ablating and injecting device 154 has an end surface 170 and an outlet portion 172. Outlets 62' and 168 may be substantially coplanar with end surface 170.

Referencing FIG. 16, exemplary laser energy and medicament source 152 may include a laser 1 10', a drive motor 1 12', a control unit 1 14', a user interface 1 16', and a coupler 1 18' as described above. Source 152 may also include a medicament supply 174 for providing medicament M and an injection unit 176 connected to supply 174, both of which are connected to control unit 1 14'. A coupler 178 connects lines from laser optics 120' and injection unit 176 into the unitary ablating and injecting device 154.

Analogous to optical fiber 56 described above, exemplaiy ablating and injecting device 154 is rotatable about an axis of rotation E and translatable between an advanced position and a retracted position. With additional reference to FIGS. 17A and 17B, system 1 50 may form a channel 138 in myocardium 132, either partially through the myocardium or completely through the myocardium. In accordance with the present invention, as distal portion 172 of ablating and injecting device 154 retracts from the advanced position to the retracted position, as shown by arrow B, control unit 1 14' activates injection unit 176 to inject medicament M from supply 174 into delivery member 158 and through outlet 168 into channel 138, as shown in FIG. 17A. When device 154 is in the retracted position and handpiece 54' is moved away, a discrete amount 179 of medicament is left within channel 138, as shown in FIG. 17B. The discrete amount 179 may partially or fully fill channel 138 The procedure may be repeated a plurality of times at different locations in the myocardium 132, thereby seeding the myocardium with medicament such as angiogenesis-promoting growth factor. Exemplary injection unit 176 may inject medicament through the use of hydraulics, pneumatics, aerosol, or other means.

In addition, injection unit 176 may be configured as an injection jet nozzle which utilizes high pressure to create a fluid column of medicament for injection into tissue. A jet injector may also be used to form a hole in or through tissue with high-pressure fluid (which may contain medicament), either by tearing (or expanding) the tissue or by removing the tissue, or a combination of both. The jet injector may be configured to deliver medicament to the tissue while forming the hole or channel therein.

Regarding the coupling of ablating and injecting device 154 to laser energy and medicament source 152, reference is made to FIGS. 18 and 19 in which an exemplary embodiment of a coupling assembly 180 is illustrated. Exemplary coupling assembly 180 includes a housing 182 which is adapted to receive a reel 184 in a rotatable and sealed relationship Reel 184 includes a passage 1 86 foi med axially thei ethi ough in which ablating and injecting device 1 54 is secui ely i eceived Reel 184 also includes an annular channel 1 88 and a through hole 190 extending between passage 186 and channel 1 88 Delivei y membei 158 extends from device 154 into through hole 1 0 to be in communication with channel 1 88 A feeding tube 192 extends between a port 1 4 of housing 1 82 and the medicament injection and supply units 176 and 174

A plurality of o-nngs 196 may be used to seal l eel 184 within housing 182, device 1 4 within passage 186, and deliveiy membei 1 58 within thi ough hole 190 Rings 196 may be low- fπction Teflon* seals Specialized couplings, such as a rouhy-Borst valve coupling, may be used to connect device 154 to ieel 184 Housing 182 may include sti ucture such as stops to limit the axial translation of i eel 184 Although exaggerated in the di wings, tolei ances between reel 1 84 and housing 1 82 may be on the oi dei of less than about 0 005 inch In addition, housing 1 82 may be of a two-piece design ith two halves hinged together to allow easy access to the inside of the housing Coupling assembly 180 allows ablating and injecting device 1 54 to l otate about rotational axis E under power fi om drive unit 1 12' while leceivmg lasei eneigy and medicament For example, device 1 54 may be dnven about 40 i evolutions in one dn ection (yielding the advanced position), and then dnven about 40 i evolutions in the othei dn ection (yielding the i en acted position) Because of the secure coupling with device 1 54, i eel 1 84 is dnven by device 154 to rotate about axis E, that is device 154 may act as a di ive shaft When it is desn ed to deliver medicament to tissue, injection unit 176 injects medicament thi ough tube 1 2 (which is indicated by an ow M) and into a space 198 defined within channel 188 and between i eel 1 84 and housing 1 82 Medicament is accordingly urged and/oi injected into the lumen 164 of deliv ery member 1 58 Medicament may be continuously injected into deliveiy lumen 158 while I eel 184 i otates As desci ibed above, the injection of medicament into delivery lumen 1 58 may be limited to when device 154 is retracting

With general reference to FIG 13, rathei than coupling deliveiy membei 158 to medicament supply 174 at source system 1 52, exemplaiy handpiece 54' may include an assembly foi injecting medicament into deliveiy member 1 8 (not shown) Foi example, a pr essur e capsule, such as a C02 capsule, may inject medicament into the inlet 166 of lumen 164 and out of the outlet 168 Deliveiy member 158 may be coiled within handpiece 54' when m the l eti acted positioned, and may then uncoil while being dnven to the advanced position In the embodiment with an injection assembly at

2 S handpiece 54', deliveiy membei 158 may have a relatively short ovei all length as the handpiece is positioned at or near the tissue targeted to leceive medicament

Alternative configuiations of the ablating and injecting device of the piesent invention are shown in FIGS 20 and 21 Referencing FIG 20, exemplary ablating and injecting device 154' includes an optical fiber 156' and a deliveiy member 1 8' molded together into a unitary structure with cladding 160' Exemplaiy delivery member 158' may be ciescent shaped in cioss-section, as shown As discussed above, the diametei du of the outlet of optical fiber 156' is pieferably at least one half of the diametei d of the end suiface 170' of device 154' For example, diameter do may be about 06 mm and diametei d^5 may be about 10 mm Accoidingly, as device 154' rotates about axis E, laser eneigy emitted fiom optical fiber 156' ablates tissue along the entne radial sweep of axis E, theieby foiming a channel of about 10 mm in diametei, which is described above (see FIG 8)

Referencing FIG 21, exemplaiy ablating and injecting device 154" includes a pan of optical fibers 156α and 156Λ and a delivery membei 158" molded tυgethei into a unitary stiuctuie with cladding 160" Exemplaiy deliveiy membei 158' may be rectilinear shaped in cross-section, as shown The outlet of each optical fibei 156 piefeiably has a diametei d„ of appioximately one quarter of the diametei d.s of the end surface 170" of device 154' Theiefore, collectively the diametei s d0 of the optical fibei s 156 and 156Λ compnse about one half of the diametei d^ of the end surface 170" Foi example diametei d„ may be about 03 mm and diametei dt, of end surface 170" may be about 10 mm Altemativelv, any numbei of fibei s may be used in multiple-fibei device 154", such as foui 015-mm diametei fibers

Optical fiber becomes more flexible when its diameter is i educed It follows that the pan of optical fibers 156 and 156/? ofFIG 21 each with a diametei of about 03 mm aie moie flexible than the single optical fibei 156' of FIG 20 with a diametei of about 06 mm As such, device 154" is more flexible and is able to follow a moie tortuous path than device 154' Accordingly, device 154' shown in FIG 20 is useful in diiect-visualization procedures in conjunction with a handpiece as clesciibed abo e such as m mtia-opeiative oi tians-thoiacic procedures, which do not lequire the optical fibei to bend thiough tortuous paths Device I 54' shown in FIG 21 is useful in indirect-visualization pioceduies in conjunction with a cathetei and a scope, such as trans-septal and endovascular pioceduies Foi example, device 154" may be inserted into a femoral arteiy, thiough the aortic aich, and into the left ventucle to ablate tissue from the endocaidium to the epicaidium Rather than forming channels in tissue with laser ablation as described above, tissue may be removed to form channels in accordance with the present invention for medicament deliveiy by other methods, for example, by high-frequency electrical energy or radio-frequency (RF) energy. Referencing FIG. 22, an exemplary embodiment of a tissue-removal and medicament- deliveiy device 200 which uses electrical energy to remove tissue in accordance with the present invention is illustrated. Device 200 includes an electrode 202 disposed on a distal tip of the device, an insulator 204 proximal to the electrode 202, and a body 206. A delivery lumen 208 is formed axially through electrode 202, insulator 204, and body 206, and has an outlet 210 in a distal end of device 200. An alternative embodiment of an electrical-energy tissue-removal and medicament- delivery device 200' of the invention is illustrated in FIG. 23. Rather than having an axial delivery lumen, device 200' includes at least one deliveiy lumen 210 formed longitudinally through at least the body 206'. As shown in FIG. 23, two delivery lumens 212c/ and 212/; are formed through the body 206' and extend into the insulator 204' Each lumen 212 has an outlet 214 formed on a side 2 16 of device 200' In the exemplary embodiment, outlets 2 14<7 and 2 14/? may be substantially diametrically opposed within the device. Alternatively, each lumen 2 12 may have a plurality of outlets which form an array of ports on the side 216 of device 200' .

With additional reference to FIG. 24, in use, the tissue-removal and medicament-delivery devices 200 and 200' generate high-frequency electrical energy, which in turn generates an ionized plasma corona 2 16 and converts tissue 132 to gas to create a channel or hole in the tissue. A ground plate 2 1 8 may be provided such t hat tissue 1 32 is positioned between the ground plate and electrode 202 The ground plate 2 1 8 may be used to control conduction paths (shown by the dashed arrows) formed by the positively charged electrode 202, which controls the formation of channels in tissue. After holes or channels are formed in tissue, medicament such as growth factor that promotes angiogenesis may be delivered to the tissue within the hole or channel itself via the delivery lumen as described above Alternatively, with reference to FIG 25, medicament may be delivered into the walls of the hole or channel 138 and into the tissue 132 surrounding the hole or channel 138 via the delivery lumens 2 12, as indicated by arrows M Referencing FIG. 26, another exemplary embodiment of an electrical-energy tissue- removal and medicament-delivery device 200" of the invention is illustrated. Device 200" includes a cathode 220 disposed on a distal tip of the device, an insulator 204" proximal to the electrode 202, an anode 222 proximal to the insulator, and a body 206". A deliveiy lumen 208 is formed axially through the device 200" Electucal-conductmg leads (not shown) connect the cathode and anode 220 and 222 to a powei soui ce When activated, conduction paths (shown in dashed lines) between the cathode 220 and the anode 220 define the ionized plasma cor nea 216' which converts tissue to gas to foi m channels Another exemplary embodiment of a medicament-delivery system 230 of the present invention is illustrated in FIGS 27, 28, and 29 System 230 includes an ablating and injecting device 232 received within a cathetei 234 Exemplai y ablating and injecting device 232 includes a pair of optical fibei s 236a and 236b and a pair of delivei y membei s 238 and 238/? Cladding 240 configures the fibers 236 and 238 into a unitar y and cylindr ical device Optical fibei s 236 and delivery members 238 may be configui ed and function in accordance with the desci iption provided above Exemplaiy device 232 also includes i ifling tr acks 242 formed on an annulai lip 244 thereof, prefei ably at a distal end of the device and exemplai y catheter 234 includes r ifling 246 formed on an inner sui face thereof foi s dingly engaging with the i ifling tracks 242 of the ablating and injecting device 232 Accordingly, as ablating and injecting device 232 i otates, the rifling 246 ti anslates the device 232 axially within cathetei 234, between the advanced and retracted positions as descr ibed above

Exemplaiy medicament-deliver y system 230 is particulai ly useful in endovasculai procedures which may entail guiding the ablating and injecting device 232 and catheter 234 through tortuous paths to its final destination Accoi dingly, it is prefei able to maximize as much as possible the flexibility of the ablating and injecting device 232 As such, it is pi eferable for the diameters of the optical fibei s 236 to be as small as possible while still capable of carrying sufficient laser energy to ablate tissue In a pi eteu ed embodiment, the diameter of each optical fiber 236 may be about 0 25 mm The over all diametei of the device 232 may then be about 0 5 mm In an alternative embodiment of the ablating and injecting device of the pi esent invention, the medicament may be delivei ed dir ectly to the tissue suπ oundmg the channel stead of delivering the medicament into the channel oi into the tissue by way of the channel This may be advantageous whei e it is desir ble to avoid systemic administration of the medicament, which could occui thi ough washout of medicament when it is delivei ed dn ectly into the channel Vanous configui ations of this alternate embodiment are shown in FIGS 30- 40 Referencing FIG. 30, alternate head portion 100' has one or more needles 250 on the outer rim of its tissue-engaging surface for penetrating the tissue around the perimeter of the tissue channel opening. This provides access directly to the tissue surrounding the channel. The delivery device is provided with one or more medicament lumens 164' which are in fluid communication with needles 250. Needles 250 pierce the tissue around the perimeter of the channel opening and deliver medicament by way of lumen or lumens 164'. The medicament diffuses through the tissue without having to enter into the channel, thus avoiding medicament washout and the possibility of systemic deliveiy of the medicament FIG. 3 1 illustrates the end surface of head portion 1 00' having an array of needles 250 around its perimeter. FIG. 32 illustrates medicament 252 diffusing into the tissue surrounding channel 138. Other embodiments of alternate head portion 100' are illustrated in FIGS. 33 and 34. FIG. 33 illustrates head portion 100' having a nozzle or nozzles 254 around its perimeter. Nozzles 254 are adapted to atomize tne medicament when head portion 100' is placed up against the tissue surrounding the channel opening. As in the previous embodiment using needles 250, the medicament is diffused directly into the tissue and not into the channel where it can be washed out into the patient's system FIG. 34 illustrates yet another embodiment wherein head portion 100' has a port or ports 256 on the head portion perimeter for diffusing medicament directly into the tissue surrounding the channel opening.

FIGS. 35 and 36 illustrate that medicament can be provided to head portion 100' through a single lumen 164" which is in fluid communication with an annular manifold 258 which communicates through the perimeter of head portion 100' to ports 256. FIG. 37 illustrates an alternate embodiment wherein single lumen 164" has an annular geometry. Those skilled in the art will appreciate that this single lumen embodiment incorporating manifold 258 can also be utilized with nozzles 254 or needles 250. Similarly, it will be appreciated by those skilled in the art that other means for diffusing medicament directly into the tissue surrounding the channel opening can be utilized for like effect.

FIG. 38 illustrates yet another exemplary embodiment wherein at least one deliveiy lumen 264 is in fluid communication with delivery outlet 266 and at least one vacuum lumen 268 is in communication with a vacuum source ( not shown) and terminates in vacuum outlet 270. By providing a vacuum to head portion 100' through lumen 268 to outlet 270 the clinician can insure that medicament can be delivered directly to the tissue through lumen 264 and outlet 266. It will be appreciated by those skilled in the art that this embodiment could include a plurality of vacuum lumens and a pluialitv, of deliveiy lumens to maximize the effectiveness of the invention

Referencing FIG 39 an alternate cxcmplaiv. embodiment ot an electucal-eneigy tissue- removal and medicament-dehveiy device 200" is illustrated wherein the medicament can be dnectly delivered into the tissue walls and difiused into the tissue suiiounding the channel As in the embodiment of FIG 23, two deliveiy lumens 212a' and 212b' aie piovided, each having its respective outlet 214a' and 214b' In the exemj)laιy embodiment outlets 214a' and 214b' may be substantially diametucally opposed within the device In this embodiment vacuum lumens 212c' and 212d' aie piovided longitudinally thiough the body of device 200 and in communication with outlets 214c' and 214d' lespectivelv Outlets 214c' and 2I4d' may also be diameti ically opposed to each othei Vacuum lumens 212c and 212d' ai e m communication with a vacuum souice (not shown) which piovides a vacuum thiough lumens 212c and 212d to outlets 214c' and 214d' to di w the tissue channel wall up against outlets 214c' and 21 cl ' Due to their proximity, sufficient vacuum can be piovided to also dia the tissue wall up against outlets 214a' and 214b' Medicament 252 can then be piovided thiough deliveiy lumens 212a' and 212b' to outlets 214a' and 214b' and dnectly into the tissue wall of the channel as illustiated in FIG 40 In the embodiment shown outlets 21 la and 214b' aie distal to outlets 214c' and 214d' Howevei, it is also possible to configuie the outlets so that 214c' and 2 I4d outlets aie distal to 214a' and 214b' outlets and to configuie the deliveiy and vacuum lumens accordingly As is the case with the embodiment of TIGS 30-38 this embodiment also peimits medicament to be diffused into the tissue suiiounding the channel without having systemic washout of the medicament

In addition to lemovmg tissue to foim holes oi channels b lasei ablation or bv, high- frequency electiical eneigy, holes oi channels mav. be loimed in tissue mechanically with hot tips oi biopsy needles, ultrasonicalh oi h\dιaulιcally with high-piessuie watei Fhe medicament can be growth factor, which may take many foims Toi example, giowth factoi may be delivered as a protein solution Alternatively, giowth factor mav be combined with a fibiin collagen or plasma to form a cellular matrix gel Giowth factoi

also be mixed into a semi-solid using a biocompatible matrix Further, giowth factoi may be delivei ed to tissue in an atomized foi under pressuie The medicament can also be a gene that encodes foi said giowth factoi oi any othei theiapeutic agent or gene therapy agent that piomotes angiogenesis oi an theiapeutic agent foi the treatment of cardio asculai disease Whatevei the foim may be the angiogenesis-promoting growth-factor solution is administered through the deliveiy lumen(s) to enhance and accelerate the angiogenic process. The growth factor solution may be driven into the channel and/or tissue using, for example, a pneumatic system, a mechanical system (e.g., a syringe-type system with a plunger), a hydraulic system (e.g., using fluids or gas), or a gravitational system. Those skilled in the art will understand that the embodiments of the present invention described above exemplify the present invention and do not limit the scope of the invention to these specifically illustrated and described embodiments. The scope of the invention is determined by the terms of the appended claims and their legal equivalents, rather than by the described examples. In addition, the exemplary embodiments provide a foundation from which numerous alternatives and modifications may be made, which alternatives and modifications are also within the scope of the present invention as defined in the appended claims
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Clasificaciones
Clasificación internacionalA61B17/22, A61B17/32, A61B18/20, A61B18/12, A61B17/00, A61M25/00, A61B18/14, A61B18/24
Clasificación cooperativaA61B2018/1425, A61B2017/00247, A61B18/24, A61B18/1477, A61B17/3203, A61B2017/22082, A61B2018/00392, A61B18/1492
Clasificación europeaA61B18/24
Eventos legales
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