WO1985004324A1

WO1985004324A1 - Bioprosthetic conduits

Info

Publication number: WO1985004324A1
Application number: PCT/GB1985/000129
Authority: WO
Inventors: William Henry Wain
Original assignee: Wessex Medical Group Limited
Priority date: 1984-03-31
Filing date: 1985-03-29
Publication date: 1985-10-10
Also published as: GB2156677A; AU4154185A; EP0175740A1; GB8408384D0

Abstract

A bioprosthetic conduit comprising an animal ureter, for example, the ureter from a pig, which is employed as a remplacement blood vessel, for example, as a replacement for a human coronary artery. The ureter is subjected to a fixation treatment while in a distended condition sufficient to remove the convoluted internal surface thereof to give a substantially smooth internal surface.

Description

BIOPROSTHETIC CONDUITS

The present invention relates to bioprosthetic conduits comprising animal ureters, and in particular to such conduits when employed as replacement blood vessels, and to methods of preparing such conduits.

Inefficient human arteries, especially coronary arteries, are commonly replaced/bypassed with other arteries or veins taken from the patient, typically the carotid artery or saphenous vein, or with arteries or veins from other human donors or human post mortem material. Human umbilical arteries and veins have also been used as well as non-human animal arteries and veins from, for example, sheep and cows. Also, wholly artificial conduits comprising knitted synthetic fibre fabrics or cast plastics materials have been employed.

So far, none of these "substitute" arteries has proved particularly satisfactory for one or more of a variety of reasons, but essentially because of the presence along the length of the replacement conduit of collateral or branch conduits which require sealing in natural substitutes, and the unacceptable build up of neointimal hyperplasia that is liable in the case of wholly artifical conduits.

Thus, since the advent of coronary artery replacement surgery in the late 1960's, the object and practice has traditionally been to replace existing blood vessels with other blood vessels, with the exception in recent years of the limited use of some wholly artifical conduits; and because of the known disadvantages referred to above, considerable, but so far unsuccessful efforts, have been expended in trying to minimise and/or avoid these problems. In the present invention, the disadvantages described above with respect to existing substitute arteries have been effectively and unexpectedly overcome, by a totally different approach to the selection of suitable replacement conduit material. Thus, the present invention provides a bioprosthetic conduit comprising an animal ureter which has been subjected to a fixation treatment while in a distended condition sufficient to expand the ureter to give a substantially smooth internal surface thereto.

The Applicants have also found that platelet aggregation, fibrin deposition and neointimal hyperplasia may be advantageously influenced by prior treatment of the bioprosthetic conduit with glycerol.

Preferably, ureters taken from pigs are employed, but ureters from other animals, such as sheep and calves, may also be mentioned. Pig ureters can provide a 25-30 cm conduit length free from collaterals, with an average internal diameter of 2-6 mm and a corresponding outside diameter of 3-7 mm.

The invention also provides a method of preparing a bioprosthetic conduit comprising an animal ureter in which the ureter is subjected to a fixation treatment while in a distended condition sufficient to expand the ureter to give a substantially smooth internal surface thereto.

Preferably, the fixation treatment employed is based on the use of gluteraldehyde solution. An essential feature of the present invention is the application of the fixation treatment while the ureter is in a distended, open condition. In the relaxed condition the ureter is closed and the internal surface thereof highly convoluted. Before the fixation treatment the ureter must be distended so as to expand its internal surface to substantially remove the convolutions to give a substantially smooth surface.

The following example of the present invention is not to be construed as limiting the invention.

Freshly removed pig ureters are stripped of exterior fat and thoroughly washed through with isotonic saline (0.9 % sodium chloride) at 4 °C. Each ureter is then mounted and secured on a bell-ended cannular, flushed through with glycerol and left immersed in glycerol for 7 days. The glycerol is washed from the ureter by an isotonic phosphate buffer solution of pH 7.4. The distal ends of the ureters are then secured and a pressure of 50 mm mercury is applied to the buffer solution to distend the ureters. Alternatively, the ureters may be cannulated at both ends and buffer solution passed therethrough under a pressure of 50 mm mercury to distend the ureters. In both cases the ureters are held in a straight position. Under a pressure of 50 mm mercury the ureter wall is expanded and the ureter opened to provide a continuous hole therethrough. Such expansion has the effect of substantially removing the internal surface convolutions of the ureter to provide a substantially smooth internal surface.

The distended ureters are then totally immersed vertically in a bath of the phosphate buffer solution using small weights to maintain the ureters in the vertical position. An overflow from the buffer reservoir to the bath ensures the circulation of the buffer solution .

The bath is then charged with sufficient 25 % gluteraldehyde solution to achieve a final concentration in the bath of 0.2 %, and the distended ureters are allowed to fix therein for at least 18 hours, during which time the gluteraldehyde solution is under circulation. After fixing, the distended ureters with substantially smooth internal surfaces, are sterilised by placing in a 4 % formaldehyde solution for 24 hours.

Hydrodynamic tests have established that the fixed ureters according to the present invention will withstand a pressure of 1500 mm mercury - well above the pressure normally experienced in human arteries (approximately 150 mm Hg).

Experimental implantation in dogs has proved successful, demonstrating no immediate thrombus formation, or restriction of the blood flow due to the innate condition of the bioprosthetic conduit.

Claims

1. A bioprosthetic conduit comprising an animal ureter which has been subjected to a fixation treatment while in a distended condition sufficient to expand the ureter to give a substantially smooth internal surface thereto.

2. A conduit as claimed in claim 1 c omprising a non-human ureter.

3. A conduit as claimed in claim 2 comprising a pig ureter.

4. A method of preparing a bioprosthetic conduit comprising an animal ureter in which the ureter is subjected to fixation treatment while in a distended condition sufficient to expand the ureter to give a substantially smooth internal surface thereto.

5. A method as claimed in claim 4 in which a non-human ureter is used.

6. A method as claimed in claim 5 in which a pig ureter is used.

7. A method as claimed in any one of claims 4 to 6 in which the ureter is pre -treated with glycerol.

8. A method as claimed in any one of claims 4 to 7 in which the ureter is treated with a glutαraldehyde solution.

9. A bioprosthetic conduit substantially as hereinbefore described with reference to the example of the invention.

10. A method of preparing a bioprosthetic conduit substantially as hereinbefore described with reference to the example of the invention.