CN103284693A

CN103284693A - Instrument for locating and identifying nerves in vessel wall, and application method thereof

Info

Publication number: CN103284693A
Application number: CN201310070218XA
Authority: CN
Inventors: 王捷
Original assignee: SUZHOU SYMAP MEDICAL Ltd
Current assignee: SUZHOU SYMAP MEDICAL Ltd
Priority date: 2012-08-24
Filing date: 2013-03-06
Publication date: 2013-09-11
Anticipated expiration: 2033-03-06
Also published as: KR101590005B1; EP2887900A1; AU2013305279B2; WO2014029355A1; EP2887900B1; CN103284693B; JP6574134B2; AU2013305279A1; CN103271766A; JP2015526177A; CN103271766B; KR20150083076A; EP2887900A4; CN203138452U

Abstract

The present invention provides an instrument for locating and identifying nerves in a vessel wall. The instrument comprises (a) a device for applying energy to the vessel wall; (b) an energy source for supplying energy applied to the vessel wall to the device (a), wherein the energy source is connected with the device (a) through a circuit; (c) a sensor for detecting or sensing physiological signals generated by a body, wherein sensor can detect or sense the physiological signals generated after the device (a) applies the energy to the vessel wall; (d) a calculating device for analyzing the physiological signals, wherein the calculating device is connected with the sensor (c) through a circuit and analyzes the signals obtained by the sensor; (e) a display doe displaying the analyzed results, wherein the display is connected with the calculating device (d) through the circuit and displays the analyzed results of the signals. The invention also provides an application method of the instrument and a method capable of locating and identifying functional nerves in the vessel wall.

Description

Neural instrument and using method in a kind of location and the identification blood vessel wall

The application requires the priority of the international patent application sequence number PCT/IB2012/054303 of submission on August 24th, 2012, and the priority of the international patent application sequence number PCT/IB2012/054310 that submitted on August 24th, 2012.

Technical field

The present invention relates to by applying energy accurately and accurately locate and identify in the blood vessel wall or the method for adventitia epineural.The present invention also relates to by applying energy accurately and accurately locate and identify in the blood vessel wall or instrument and the using method of adventitia epineural and clear this information of demonstration.

Background technology

In (comprise in the blood vessel and adventitia on) various innervations are often arranged on the blood vessel wall in human body.It is to observe directly in the complete vessel lumen of living person's body with naked eyes that nerve in these blood vessel wall distributes, the more impossible neural classification of directly telling in the blood vessel wall.In some cases, must know distribution and the classification of these nerves, for example, physiologist or clinician will be specific neural experiment or the treatment of doing accurately to locate for use in subsequently of certain class in the blood vessel wall.Because some nerve in the blood vessel wall is the autonomic nerve that can cause human body whole body physiological reaction, thus in theory can be by apply neural site in the accurate localization of blood vessel wall of energy to these nerves.When energy is applied to certain site on the blood vessel wall, monitor the physiologic parameters relevant with autonomic nervous system, as blood pressure, heart rate and muscle neural activity, whether the change of these parameter values has autonomic nerve to exist around can reflecting this site.Sympathetic nerve and parasympathetic nervous can produce opposite effect usually in the autonomic nervous system in human body, as the effect to blood pressure and heart rate.Therefore, after successfully monitoring the physiologic parameters relevant with autonomic nervous system, the positive negative direction that changes based on these parameters more can be segmented sympathetic nerve and the parasympathetic nervous in the blood vessel wall.Consideration at above-mentioned physiology principle and phenomenon, the invention provides a method of accurately locating and identify blood vessel wall epineural site, an accurate location and identification blood vessel wall epineural site also instrument and the using method of clear this information of demonstration further are provided.

Summary of the invention

The invention provides a kind of by apply energy in the human vas wall whether to have sympathetic nerve and parasympathetic method of function in the identification blood vessel wall.This method comprises one or more steps: applying energy before blood vessel wall, recording the baseline of one or more physiologic parameters; Apply energy to blood vessel wall; The physiologic parameters that detection applies behind the energy changes; According to a series of numerical value of presetting by experiment classification is carried out in the variation of the physiologic parameters of generation; Determine according to the grade that physiological parameter changes whether the zone that applies energy exists sympathetic nerve or parasympathetic nervous on every side.

In one embodiment, described blood vessel is to comprise arteriorenal tremulous pulse.

In certain embodiments, the energy that is applied to arterial wall can produce stimulation to nerve.

In one embodiment, physiologic parameters comprises blood pressure, heart rate, heart rate variability, cardiac electrical activity, musculation, skeleton neural activity, action potentials of cells, with biochemical indicators such as epinephrine, norepinephrine, renin angiotensin II and vasopressins, and these physiologys change other detectable reactions such as pupillary reflex, electromyogram and the vasoconstriction etc. that cause.

In certain embodiments, stimulate some zone on the blood vessel wall, blood pressure and heart rate are raise, illustrated that sympathetic nerve distributes, on the contrary, reduce as if blood pressure and heart rate when stimulating vascular wall area, or heart rate reduces separately, illustrates that then there is parasympathetic nervous in this zone.As if blood pressure and heart rate no change, illustrate that then this zone does not exist sympathetic nerve or parasympathetic nervous when stimulating vascular wall area.

In one embodiment, if physiologic parameters obviously departs from baseline when applying energy, illustrate that then described energy accurately has been applied to the target nerve of blood vessel wall.

In one embodiment, there is neural the distribution in certain zone on the blood vessel when having confirmed applying by above method before the energy, and after applying energy, physiologic parameters such as blood pressure and heart rate no longer change when stimulating this site again, then think no longer there is the nerve that can influence the whole body physiological reaction herein.

The present invention also provides the neural instrument that distributes and show this result in a location and the identification blood vessel wall.This instrument comprises that one or more energy that apply are to the device of blood vessel wall; One or more energy sources that the energy that applies to blood vessel wall is provided, one or more sensors that receive the physiologic parameters signal; One or more accountants of analyzing the signal that receives from sensor; But one or more display analysis results' indicator or panel.

In one embodiment, applying energy device is the device that scalable applies energy intensity.

In another embodiment, the energy that applies is one or more in electric energy, radio-frequency (RF) energy, mechanical energy, ultrasonic, radiation, luminous energy and the heat energy.

In certain embodiments, described sensor can detect physiologic parameters, comprise blood pressure, heart rate, heart rate variability, be selected from epinephrine, biochemical indicator such as norepinephrine, renin angiotensin II and vasopressin and cardiac electrical activity, musculation, skeleton neural activity, action potentials of cells and other detectable reactions of producing because of above-mentioned variation, as pupillary reflex, electromyogram and vasotonia etc.

In certain embodiments, can utilize the existing technology in this area to detect the corresponding signal of these physiologic parameters.

In another embodiment, the device that the physiologic parameters signal is analyzed is a microcontroller or computer.

In one embodiment, energy source is integrated into and can applies energy to the device of blood vessel wall.

In one embodiment, analysis result is with the indicator for displaying of different colours.The zone that has sympathetic nerve to exist represents that with green the zone that has parasympathetic nervous to exist is represented with redness.In another embodiment, analyzed data show is on a digital visible surface plate.

In one embodiment, a cover indicator or panel can be put in the intrasystem device, as the energy bringing device.In certain embodiments, a cover indicator or panel can be used as the independently unit in the system and exist.

The present invention further provides the method for using described instrument.

Description of drawings

Fig. 1 illustrates the sketch map of an embodiment that can locate and identify the instrument that has the neural of function in the blood vessel wall and show this result among the present invention.Native system comprises can apply energy to the device 101 of blood vessel wall; The energy source 102 of energy can be provided to device 101; Can detect the sensor 103 of physiologic parameters signal; Can analyze the accountant 104 of the data of receiving from sensor 103; The indicator 105 that can show the analysis result that obtains from accountant 104.

Figure 2 shows that by apply energy in the human vas wall whether to have the sympathetic nerve of function and the step among embodiment of parasympathetic method in the identification blood vessel wall.The chart on the right is depicted as issuable physiologic parameters signal among the figure.

The minimum and maximum variation of caused systolic arterial pressure after Fig. 3 A shows and apply electric energy in left renal artery (LRA) (ASP is unit with mmHg).The base line measurement control value is to apply the preceding systolic arterial pressure of electric energy.

Caused auterial diastole was pressed the minimum and maximum variation of (ADP is unit with mmHg) after Fig. 3 B showed and apply electric energy in left renal artery (LRA).The base line measurement control value is to apply the preceding auterial diastole of electric energy to press.

The minimum and maximum variation of caused mean arterial pressure after Fig. 3 C shows and apply electric energy in left renal artery (LRA) (MAP is unit with mmHg).The base line measurement control value is to apply the preceding mean arterial pressure of electric energy.

The minimum and maximum variation of caused heart rate after Fig. 3 D shows and apply electric energy in left renal artery (LRA) (HR, the per minute heart beating is unit).The base line measurement control value is to apply the preceding heart rate of electric energy.

The minimum and maximum variation of caused systolic arterial pressure after Fig. 4 A shows and apply electric energy in right renal artery (RRA) (ASP is unit with mmHg).The base line measurement control value is to apply the preceding systolic arterial pressure of electric energy.

Caused auterial diastole was pressed the minimum and maximum variation of (ADP) after Fig. 4 B showed and apply electric energy in right renal artery (RRA).The base line measurement control value is to apply the preceding auterial diastole of electric energy to press.

Caused mean arterial pressure (MAP) changed after Fig. 4 C showed and apply electric energy in right renal artery (RRA).The base line measurement control value is to apply the preceding systolic arterial pressure of electric energy.

The minimum and maximum variation of caused heart rate (HR) after Fig. 4 D shows and apply electric energy in right renal artery (RRA).The base line measurement control value is to apply the preceding heart rate of electric energy.

Shown in Figure 5 when some site applies electric energy in renal artery heart rate reduce.

Fig. 6 A shows when applying electric energy four times respectively in left renal artery (LRA) tube chamber, the variation of caused systolic arterial pressure (ASP) each time.

Fig. 6 B shows when applying electric energy four times respectively in left renal artery (LRA) tube chamber, and caused auterial diastole is pressed the variation of (ADP) each time.

Fig. 6 C shows when applying electric energy four times respectively in left renal artery (LRA) tube chamber, the variation of caused mean arterial pressure (MAP) each time.

Fig. 6 D shows when applying electric energy four times respectively in left renal artery (LRA) tube chamber, the variation of caused heart rate (HR) each time.

Fig. 7 A shows when applying electric energy four times respectively in right renal artery (RRA) tube chamber, the variation of caused systolic arterial pressure (ASP) each time.

Fig. 7 B shows when applying electric energy four times respectively in right renal artery (RRA) tube chamber, and caused auterial diastole is pressed the variation of (ADP) each time.

Fig. 7 C shows when applying electric energy four times respectively in right renal artery (RRA) tube chamber, the variation of caused mean arterial pressure (MAP) each time.

Fig. 7 D shows when applying electric energy four times respectively in right renal artery (RRA) tube chamber, the variation of caused heart rate (HR) each time.

The specific embodiment

The invention provides and a kind ofly can locate or identify the instrument that is positioned at the nerve on blood vessel wall or the adventitia, it is characterized in that described instrument comprises: the device that (a) applies energy to blood vessel wall; (b) be used for providing to the device of (a) energy source of the energy that applies to blood vessel wall, described energy source connects the device of (a) by circuit; (c) be used for to survey or the sensor of the physiological signal that perception is produced by body, the device that the detectable or perception of described sensor goes out (a) applies behind the energy and the physiological signal that causes to blood vessel wall; (d) for the accountant of analyzing physiological signal, described accountant connects the sensor of (c) and the signal that analyte sensors obtains by circuit; (e) for display analysis result's indicator, described indicator connects the accountant of (d) by circuit and shows the analysis result of described signal.

At an embodiment, the device of described (a) comprises ablation catheter, and described ablation catheter can further have the mapping function.

At another embodiment, the device of described (a) is the device that applies radio-frequency (RF) energy or high intensity focused ultrasound.

At some embodiment, the device of described (a) is the device that can apply energy, and described energy is selected from electric energy, radio frequency, mechanical energy, ultrasonic, radiation, luminous energy and heat energy.

At an embodiment, described sensor is for surveying or the sensor of the physiological signal that perception is produced by the healths of human body or other animals.

At an embodiment, described sensor is to survey or perception blood pressure, heart rate, heart rate variability the sensor of cardiac electrical activity, muscle neural activity, skeleton neural activity, cell animal current potential, pupillary reflex, electromyogram, vasoconstriction, epinephrine level, noradrenaline levels, renin angiotensin II level or vasopressin level.

At an embodiment, described accountant is the accountant that can determine the positive negative direction of physiological parameter variation.

In one embodiment, energy source is integrated into and can applies energy to the device of blood vessel wall, and the energy that applies to blood vessel wall is provided for described device.

At an embodiment, device (a) is the device that scalable applies energy intensity.

At an embodiment, described accountant is microcontroller or computer.

At an embodiment, described indicator is with numeral, literal, symbol, color, waveform or above any compound mode display analysis result.

Fig. 1 has illustrated one embodiment of the present of invention, and its uses blood pressure and heart rate as the physiologic parameters of identification nerves reaction.This system comprises one or more energy that apply to the device 101 of arterial wall, and it is connected by circuit with energy source 102.This system also comprises the sensor 103 that can detect physiological, and it is connected by circuit with the accountant 104 of analytical physiology signal.The indicator 105 that can show accountant 104 analysis results, it is connected by circuit with device 104.In this enforcement illustration, device 101 is the conduits that mapping arranged and melt dual-use function, and is placed on the renal artery intracavity.At least one electrode clear and definite site in the renal artery wall in the device 101 contacts with the renal artery wall, and the energy that energy source 102 sends can be applied to the electrode contact point.When the electrode of device on 101 applied energy and contact the site to the electrode of arterial wall, sensor 103 can detect the variation of blood pressure and/or heart rate.The signal that sensor 103 sends is transported to accountant 104, thereby analyzes in digital form and determine that this signal is to be produced or produced by parasympathetic nervous by sympathetic nerve, does not perhaps have the nerve of function.Indicator 105 will show the analysis result that obtains from accountant 104 then.

In one embodiment of the invention, device 101 is that an invasive or intervention property device can produce damage or the device of wound, and it can enter tremulous pulse, and can apply energy to endarterial nerve.In a different enforcement illustration, device 101 is a single electrode conduit or multiple electrode catheter.

In one embodiment, installing 101 energy that are applied in the blood vessel wall is that Come is from energy source 102.Implement in the illustration at another, implement in the illustration at another, energy source 102 is integrated into applies energy device 101, can apply energy to arterial wall by human body.In other implemented illustrations, energy source 102 was multichannel energy sources, and can be respectively independent applies energy to the interior clear and definite site of arterial wall.Implement in the illustration at another kind, energy source 102 is single channel energy sources, at every turn only to apply primary energy.Implement in the illustration at another kind, the intensity that applies energy by energy source 102 is adjustable, and effect that can be different to the generation of target nerve is as stimulating or melting.In other implemented illustrations, the energy of energy source 102 emissions was one or more in radio frequency, electric energy, mechanical energy, ultrasonic, radiation, luminous energy and the heat energy.

In one embodiment, sensor 103 can detect physiological, comprise biochemical indicators such as blood pressure, heart rate, heart rate variability, epinephrine, norepinephrine, renin angiotensin II and vasopressin, with cardiac electrical activity, musculation, skeleton neural activity, action potentials of cells, and other detectable reactions such as pupillary reflex, electromyogram and vasoconstriction.Implement in the illustration at other, sensor 103 can contact or be not in contact with the above signal of external detection with any position of human body.In another kind was implemented illustration, sensor 103 can be positioned in human body and be in contact with it in some lumen of vessels or in its vicinity, to detect the above signal, as renal artery, femoral artery or other blood vessels.In another kind was implemented illustration, sensor 103 also can be from uniting the sensor of another instrument of use with the present invention.

In one embodiment, accountant 104 is one or more microcontroller or computers that can carry out numerical analysis to the signal that sensor 103 directly or indirectly produces.

In one embodiment, indicator 105 is one or more digitizing tablets for display device 104 analysis results.In another embodiment, one or more analysis results that a plurality of sites obtain on the blood vessel wall can show in indicator 105 simultaneously.In further embodiments, indicator 105 also can show the one or more physiological signals that obtain from sensor 103; The information relevant with energy that obtains from energy source is as electric current, frequency, voltage; The information relevant with tissue-electrode contact interface is as electrical impedance; And with device 101 relevant information, as temperature.In certain embodiments, indicator 105 has the lamp of a series of different colours, and every kind of lamp can clearly be represented sympathetic nerve, parasympathetic nervous or not have the nerve of function.In another kind of embodiment, indicator 105 can show from accountant 104 obtain with literal, color, sound or the represented result of above combining form.

In certain embodiments, accountant 104 and indicator 105 can be combined to an independent device, implement in the illustration at other, and accountant 104 and indicator 105 can be combined into one with energy source 102.

Implement in the illustration at another kind, sensor 103, accountant 104 and indicator 105 are with respect to device 101 and energy source 102 independent existence.But therefore sensor 103, accountant 104 and indicator 105 also other external methods that apply energy in energy or the body that apply be used, as high intensity focused ultrasound.

The present invention also provides a kind of and has used the described instrument of described instrument to locate or identify to be positioned at the method that the nerve of function is arranged on blood vessel wall or the adventitia, it is characterized in that may further comprise the steps: (a) apply the one or more sites of energy on the blood vessel wall of body with the device that applies energy, make with blood vessel in sympathetic nerve or the active relevant one or more physiologic parameters of parasympathetic nervous change; (b) detect one or more physiological with sensor after applying energy at every turn; Physiological parameter when (c) the one or more physiological that obtain with calculating device analysis sensor, and contrast nerve are not accepted energy; (d) analysis result of usefulness indicator for displaying accountant.

At an embodiment, described body is the health of human body or other animals.

At an embodiment, described blood vessel is tremulous pulse, comprises renal artery.

At an embodiment, described nerve is relevant with baroreflex.

At an embodiment, described energy is selected from electric energy, radio-frequency (RF) energy, mechanical energy, ultrasonic, radiation, luminous energy and heat energy.

At an embodiment, described physiologic parameters is selected from blood pressure, heart rate, heart rate variability, cardiac electrical activity, muscle neural activity, skeleton neural activity, cell animal current potential, pupillary reflex, electromyogram, vasoconstriction, epinephrine level, noradrenaline levels, renin angiotensin II level and vasopressin level.

At an embodiment, when the accountant analysis showed that physiologic parameters does not change, indicator can show the information that does not have the nerve that function is arranged.

At an embodiment, when the accountant analysis showed physiologic parameters generation significant change, indicator can show the information that has the nerve that function is arranged.

At an embodiment, indicator shows further that according to the positive negative direction of described physiologic parameters significant change what exist is sympathetic nerve or parasympathetic information.

The present invention further provides a kind of method that can locate or identify the nerve that function is arranged in the blood vessel wall, it is characterized in that may further comprise the steps: (a) energy is applied to one or more sites on the blood vessel wall of body, make with blood vessel in sympathetic nerve or the active relevant one or more physiologic parameters of parasympathetic nervous change; (b) apply at every turn and detect one or more physiologic parameters behind the energy, and the physiological parameter that contrast is neural when not accepting energy; Wherein in step (b), if physiologic parameters does not change and then illustrates and applying the nerve that the energy site does not have function, if physiologic parameters generation significant change then illustrates and applying the nerve that the energy site has function, and the positive negative direction that changes of physiologic parameters determines to apply, and the energy site exists is sympathetic nerve or parasympathetic nervous.

At an embodiment, described nerve is relevant with baroreflex.

At an embodiment, described body is the health of human body or other animals.

At an embodiment, described energy comprises electric energy, radio-frequency (RF) energy, mechanical energy, ultrasonic, radiation, luminous energy and heat energy.

Fig. 2 flow chart is depicted as determines whether the interior appointed area of arterial wall exists the step of functional sympathetic nerve or parasympathetic method.

In step 1, the physiological that obtains from sensor 103 with accountant 104 continuous records, thus obtain a reliable baseline, can judge any change of this signal at any time.

Apply the zone (step 2) that energy contacts with its electrode to the arterial wall by installing 101 then.Sensor 103 causes that any physiology changes after can detecting and applying energy, and this variation is recorded with signal form, is sent to accountant 104 (step 3) then.

In step 4, accountant 104 can be determined the situation that departs from respect to the physiological of baseline in the step 1, can be according to the situation that departs from respect to baseline in step 5, determine the type of the nerve that distributes in the arterial wall.

In one embodiment, sensor 103 detected physiological comprise following one or more: biochemical indicators such as blood pressure, heart rate, heart rate variability, epinephrine, norepinephrine, renin angiotensin II and vasopressin, with cardiac electrical activity, musculation, skeleton neural activity, action potentials of cells and caused observable human response more than other, as pupillary reflex and vasotonia.

In one embodiment, the energy intensity that applies in step 2 is adjustable.

In certain embodiment, can utilize other external device (ED)s to detect physiological, and before applying energy, be imported in the device 104, the baseline that forms before the alternative 104.

In one embodiment, in step 2, in applying energy process or detect the variation of physiologic parameters afterwards.In another kind of embodiment, the variation of physiologic parameters shows with the form of numerical value or waveform.Implement by the baseline of subtraction step from signal 1, to assess the situation that departs from respect to baseline in the step 1 in the illustration at other.

In one embodiment, can obtain a series of numerical value default according to experiment from a series of tests.In certain embodiments, when applying energy to the arterial wall during certain zone, if heart rate increases by 10 times/minute or above and/or blood pressure increase 6mmHg or more than, think that then this zone has sympathetic nerve to exist.In another kind of embodiment, apply energy to the arterial wall during certain zone, heart rate is reduced by at least 5 times/minute and/or blood pressure reduces 2mmHg at least, thinks that then this zone has parasympathetic nervous to exist.

In further embodiments, the result of step 5 shows in indicator 105.

In one embodiment, this method can be passed through the effect of sympathetic nerve and parasympathetic nervous system is regulated or the interference baroreflex, and then has the site of nerve on the identification arterial wall.Implement in the illustration at another kind, this method can determine whether the energy that applies is applied on the interior target nerve of arterial wall accurately.

In another kind of embodiment, can confirm distribution neural in the blood vessel by repeated application the method in whole blood vessel.Implement in the illustration at other, labelling to nerve distribute and can interrelate with the blood vessel three dimensional structure, this three dimensional structure is by from chromatography imaging technique, as nuclear magnetic resonance, computer x-ray tomography art or ultrasonic, the default data that obtain, thereby the image that can provide the nerve of a three-dimensional to distribute.At an embodiment, device 101 can or ultrasonicly come imaging by real-time image technology such as X ray in endovascular instantaneous position.Implement in the illustration at another kind, advanced imaging processing technology can interrelate the 3-D view of blood vessel with the instantaneous position of positioner 101, can determine the relation between neural distribution and the blood vessel three dimensional structure.

The part that does not describe in detail as yet among the present invention can be understood with reference to disclosed content in the patent document of the international patent application sequence number PCT/IB2012/054303 that submitted on August 24th, 2012 and the international patent application sequence number PCT/IB2012/054310 that submitted on August 24th, 2012.

The present invention is summarized, by can more easily understanding the present invention with reference to following example, following example only is in order to further specify some concrete aspect of the present invention, details and concrete experimental result, and the present invention is not made restriction.

Example 1

The nerve that function is arranged in location or the identification renal artery wall

Thereby this example design one change neural the distribution and the class method for distinguishing in location and the identification blood vessel wall according to apply the physiologic parameters that produces behind the energy of suitable intensity to blood vessel wall, and in acute pig is tested, verify.

Pig with 3 body weight 50-52kg of pentobarbital sodium (15mg/kg, intravenous injection) anesthesia.Monitoring systolic arterial pressure, diastolic pressure, mean arterial pressure and heart rate.Experimental design and scheme are as shown in Figure 3.

The used energy applicator of this experiment be the conduit that is used at present cardiac ablation clinically (7F, Type B, at interval 2-5-2mm,

RMT diagnoses/melts adjustable conduit, Biosense Webster, Diamond Bar, California 91765, the U.S.) and a kind of radio-frequency signal generator (STOCKERT70RF Generator, Model Stockert GmbH EP-SHUTTLE ST-3205, STOCKERT GmbH, Freiburg, Germany).

Apply electric energy in renal artery before, monitoring systolic arterial pressure, diastolic pressure, mean arterial pressure and heart rate obtain the base line measurement control value.Then some sites in the renal artery are applied electric energy and carry out electricity irritation; Begin after 5 seconds in 2 minutes time, to detect systolic pressure, diastolic pressure, mean arterial pressure and heart rate applying electric energy, with evaluation effect.Applying energy to the back blood pressure that causes of the nerve in the renal artery wall and the situation of change of heart rate by observing, the position that can cause blood pressure and changes in heart rate of discovery nerve in each animal arterial wall is all different, can in each animal, utilize the method to carry out correct positioning in these zones, can determine neural distribution the in the renal artery.

Example 2

The neural relation that distributes in physiologic parameters and the arterial wall

In order to prove that delivered energy can cause different influences with heart rate to physiological parameter such as blood pressure on the arterial wall diverse location, and these features more can utilize to identify the classification of the potential nerve of arterial wall, and this example has innerv zone to apply electric energy with a plurality of methods to the renal artery wall of pig.The detail parameters of the electric energy that applies to No. 1 pig, No. 2 pigs and No. 3 pigs is shown in table 1, table 2 and table 3 respectively.Rule of thumb, described parameter can stimulate the nerve in the arterial wall.

No. 1 pig (table 1) carries out four different stimulations respectively in left renal artery, carry out twice different stimulation in the right renal artery.The ventral aorta side of leaning at left renal artery applies twice different electricity irritation respectively: direct action is in the tremulous pulse antetheca, and another secondary action is in the tremulous pulse rear wall.Antetheca and rear wall by the kidney side at left renal artery: apply once different electricity irritation respectively, direct action is in the tremulous pulse antetheca, and another secondary action is in the tremulous pulse rear wall.Observe these stimulations to the Different Effects of blood pressure and heart rate.In right renal artery, apply an electricity irritation to arteriorenal respectively by the ventral aorta side with by the kidney side.No. 2 pigs and No. 3 pigs are adopted same stimulating method.

More than these results shown clearly for every test and used pig that the diverse location in the renal artery is applied electric energy stimulates the different variations that can cause systolic pressure, diastolic pressure, mean arterial pressure and heart rate.For example in No. 1 pig and No. 3 pigs, it is respectively 19.5mmHg and 29mmHg that left renal artery is applied that the maximum that causes systolic pressure behind the electric energy changes; The minimum change of systolic pressure is respectively 2mmHg and 1mmHg.But for No. 2 pigs, to arteriorenal be consistent by the ventral aorta side or by the variation that the kidney rear flank applies the systolic pressure that electric energy causes.In addition, the position of the minimum and maximum variation that the electricity irritation of same parameter can produce between different animals is different, and it is inconsistent that the kidney sympathetic nerve between this explanation different animals distributes.When applying electric energy to left renal artery, can observed systolic arterial pressure, the reaction of diastolic pressure, mean arterial pressure and heart rate is summarized in table 4A, 4B, 4C and 4D respectively.When right renal artery is applied electric energy, can observed systolic arterial pressure, the reaction of diastolic pressure, mean arterial pressure and heart rate is summarized in table 5A, 5B, 5C and 5D respectively.

Above test applies electric energy and stimulates and can cause elevation of the blood pressure or reduce to having the neural site that distributes of kidney through a device that places the renal artery intracavity, can cause that maybe heart rate raises or reduce, thereby sympathetic and conceptual checking that parasympathetic nervous distributes in location and the identification blood vessel wall is provided.The average data (meansigma methods+standard deviation) that calculates from table 4A-D and table 5A-D presents in Fig. 3 and Fig. 4 with the form of chart, comprises all subgraphs.

Table 1. is used for the neural kidney nerve stimulation that distributes of mapping

Table 2. is used for the kidney nerve stimulation of location kidney nerve

Table 3 is used for the kidney nerve stimulation of location kidney nerve

The variation of systolic arterial pressure (SBP) during the table 4A. electricity irritation left renal artery

The variation of diastolic pressure (DBP) during the table 4B. electricity irritation left renal artery

The variation of table 4C. electricity irritation left renal artery period average arterial pressure (MAP)

The variation of heart rate (HR/min) during the table 4D. electricity irritation left renal artery

The variation of systolic pressure (SBP) during the table 5A. electricity irritation right renal artery

The variation of diastolic pressure (DBP) during the table 5B. electricity irritation right renal artery

The variation of table 5C. electricity irritation right renal artery period average arterial pressure (MAP)

The variation of heart rate (HR/min) during the table 5D. electricity irritation right renal artery

May acting on of table 6. stimulation of renal nerve

In aforesaid test, some site in the renal artery wall applies electric energy can obviously descend heart rate under the situation that does not change blood pressure, or the degree that descends with heart rate relatively, blood pressure minimum (Fig. 5).Can be observed blood pressure, particularly diastolic pressure time and again, slight decline.Comprise all 4 physiologic parameters that detect in this experiment in 56 data points, wherein each physiologic parameters has 1 data point at least, and numerical value descends or do not change or do not have a significant change after applying energy; This accounts for 23% of all data points in this test.The nerve that these obvious physiologys of taking place when stimulating change these sites of explanation has parasympathetic characteristic, and these are different with the situation that blood pressure and heart rate rising take place when being upset in the site that sympathetic nerve distributes.Table 6 has been summed up in the past in the different researchs that comprise dog, cat and rabbit animal model, the effect that the energy that applies proper strength produces when importing the kidney sympathetic nerve into.Consistent with the present invention, studies show that at the energy that applies proper strength in the table 6 during to kidney neural, produced the situation of the effect similar to parasympathetic activity.This has shown that in the renal artery nerve, existence can be induced the nerve of parasympathetic nervous effect rather than sympathetic nerve effect, and therefore having needs also can identify such nerve.

Example 3

Guarantee accurately to apply energy to target nerve with the damage target nerve

After the research of nerve, the intensity that increases the energy that applies also is applied on same the neural site of the previous oriented renal artery wall of pig in location and identification arterial wall.In left and right renal artery, carry out four tests respectively, from the kidney side by antetheca, rear wall, upper wall, the order of lower wall moves to the ventral aorta side then; Apply position and the previous location interval≤5mm of energy, and the electrode tip of ablation catheter (conduit head end) rotates 90 ° at every turn after applying energy at every turn.Apply 5 watts energy level to left renal artery, duration 120 seconds; Apply 8 watts energy level to right renal artery, duration detected systolic arterial pressure, diastolic pressure, mean arterial pressure and heart rate in the process in 120 seconds.These data clearly are presented at different loci in the renal artery and apply energy and can make blood pressure and heart rate that different variations takes place, and then explanation as the physiology of blood pressure and heart rate etc. change and can be used as evaluation and whether accurately apply energy to the indicator of target nerve, and the evidence that the nerve distribution has individual variation in the arterial wall further is provided.

When four different loci applied energy in the renal artery of left kidney, the change of systolic arterial pressure, auterial diastole pressure, mean arterial pressure and heart rate was respectively shown in Fig. 6 A, 6B, 6C and 6D.When four different loci applied energy in the renal artery of right kidney, the change of systolic arterial pressure, auterial diastole pressure, mean arterial pressure and heart rate was respectively shown in Fig. 7 A, 7B, 7C and 7D.

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Claims

1. can locate or identify the instrument that is positioned at the nerve on blood vessel wall or the adventitia for one kind, it is characterized in that described instrument comprises:

(a) apply the device of energy to blood vessel wall;

(b) be used for providing to the device of (a) energy source of the energy that applies to blood vessel wall, described energy source connects the device of (a) by circuit;

(c) be used for to survey or the sensor of the physiological signal that perception is produced by body, the device that the detectable or perception of described sensor goes out (a) applies behind the energy and the physiological signal that causes to blood vessel wall;

(d) for the accountant of analyzing physiological signal, described accountant connects the sensor of (c) and the signal that analyte sensors obtains by circuit;

(e) for display analysis result's indicator, described indicator connects the accountant of (d) by circuit and shows the analysis result of described signal.

2. instrument according to claim 1, it is characterized in that: device (a) comprises ablation catheter.

3. instrument according to claim 2, it is characterized in that: described ablation catheter can further have the mapping function.

4. instrument according to claim 1, it is characterized in that: device (a) is the device that applies radio-frequency (RF) energy or high intensity focused ultrasound.

5. instrument according to claim 1, it is characterized in that: device (a) is the device that can apply energy, described energy is selected from electric energy, radio-frequency (RF) energy, mechanical energy, ultrasonic, radiation, luminous energy and heat energy.

6. instrument according to claim 1 is characterized in that: described sensor is for surveying or the sensor of the physiological signal that perception is produced by the healths of human body or other animals.

7. instrument according to claim 6, it is characterized in that: described sensor is to survey or perception blood pressure, heart rate, heart rate variability the sensor of cardiac electrical activity, muscle neural activity, skeleton neural activity, cell animal current potential, pupillary reflex, electromyogram, vasoconstriction, epinephrine level, noradrenaline levels, renin angiotensin II level or vasopressin level.

8. instrument according to claim 1 is characterized in that: described accountant is the accountant of the positive negative direction that can determine that physiological parameter changes.

9. instrument according to claim 1, it is characterized in that: energy source (b) is integrated into the energy device that applies of (a).

10. instrument according to claim 1, it is characterized in that: device (a) is the device that scalable applies energy intensity.

11. instrument according to claim 1 is characterized in that: described accountant is microcontroller or computer.

12. instrument according to claim 1 is characterized in that: described indicator is with numeral, literal, symbol, color, waveform or above any compound mode display analysis result.

Be positioned at the method that the nerve of function is arranged on blood vessel wall or the adventitia, it is characterized in that may further comprise the steps 13. a right to use requires 1 described instrument to locate or identify:

(a) apply the one or more sites of energy on the blood vessel wall of body with the device that applies energy, make with blood vessel in sympathetic nerve or the active relevant one or more physiologic parameters of parasympathetic nervous change;

(b) detect one or more physiological with sensor after applying energy at every turn;

Physiological parameter when (c) the one or more physiological that obtain with calculating device analysis sensor, and contrast nerve are not accepted energy;

(d) analysis result of usefulness indicator for displaying accountant.

14. method according to claim 13 is characterized in that: described body is the health of human body or other animals.

15. method according to claim 13 is characterized in that: described blood vessel is tremulous pulse.

16. method according to claim 15 is characterized in that: described tremulous pulse is renal artery.

17. method according to claim 13 is characterized in that: described nerve is relevant with baroreflex.

18. method according to claim 13 is characterized in that: described energy is selected from electric energy, radio-frequency (RF) energy, mechanical energy, ultrasonic, radiation, luminous energy and heat energy.

19. method according to claim 13 is characterized in that: described physiologic parameters is selected from blood pressure, heart rate, heart rate variability, cardiac electrical activity, muscle neural activity, skeleton neural activity, cell animal current potential, pupillary reflex, electromyogram, vasoconstriction, epinephrine level, noradrenaline levels, renin angiotensin II level and vasopressin level.

20. according to any one described method of claim 13 to 19, it is characterized in that: when the accountant analysis showed that physiologic parameters does not change, indicator can show the information that does not have the nerve that function is arranged.

21. according to any one described method of claim 13 to 19, it is characterized in that: when the accountant analysis showed physiologic parameters generation significant change, indicator can show the information that has the nerve that function is arranged.

22. according to any one described method of claim 13 to 21, it is characterized in that: indicator shows further that according to the positive negative direction of described physiologic parameters significant change what exist is sympathetic nerve or parasympathetic information.

23. the method that can locate or identify the nerve that function is arranged in the blood vessel wall is characterized in that may further comprise the steps:

(a) energy is applied to one or more sites on the blood vessel wall of body, make with blood vessel in sympathetic nerve or the active relevant one or more physiologic parameters of parasympathetic nervous change;

(b) apply at every turn and detect one or more physiologic parameters behind the energy, and the physiological parameter that contrast is neural when not accepting energy;

Wherein in step (b), if physiologic parameters does not change and then illustrates and applying the nerve that the energy site does not have function, if physiologic parameters generation significant change then illustrates and applying the nerve that the energy site has function, and the positive negative direction that changes of physiologic parameters determines to apply, and the energy site exists is sympathetic nerve or parasympathetic nervous.

24. method according to claim 23 wherein is characterized in that: described blood vessel is tremulous pulse.

25. method according to claim 24 is characterized in that: described tremulous pulse is renal artery.

26. method according to claim 23 is characterized in that: described nerve is relevant with baroreflex.

27. method according to claim 23 is characterized in that: described body is human body or or the health of other animals.

28. method according to claim 23 is characterized in that: described physiologic parameters is selected from blood pressure, heart rate, heart rate variability, cardiac electrical activity, muscle neural activity, skeleton neural activity, cell animal current potential, pupillary reflex, electromyogram, vasoconstriction, epinephrine level, noradrenaline levels, renin angiotensin II level and vasopressin level.

29. according to any one described method in the claim 23 to 28, it is characterized in that: described energy is selected from electric energy, radio-frequency (RF) energy, mechanical energy, ultrasonic, radiation, luminous energy and heat energy.