GB2180755A

GB2180755A - Methods for preparing bioprosthetic conduits

Info

Publication number: GB2180755A
Application number: GB08523724A
Authority: GB
Inventors: William Henry Wain
Original assignee: WESSEX MEDICAL GROUP Ltd
Current assignee: WESSEX MEDICAL GROUP Ltd
Priority date: 1985-09-26
Filing date: 1985-09-26
Publication date: 1987-04-08
Also published as: GB8523724D0

Abstract

A bioprosthetic conduit comprising an animal ureter, for example, a ureter from a pig, is suitable as a replacement blood vessel, for example, a human coronary artery. Preferably, the ureter is treated to remove its inner epithelial surface and subjected to a fixation treatment while in a distended condition. The distension is sufficient to remove the convoluted internal surface of the ureter to give a substantially smooth internal surface.

Description

SPECIFICATION Methods for preparing bioprosthetic conduits The present invention relates to methods for preparing bioprosthetic conduits comprising animal ureters, ureters suitable for use as bioprosthetic conduits and bioprosthetic conduits prepared according to these methods. In particular the present invention relates to such conduits when employed as replacement blood vessels.

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 artieries 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 artificial 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.

Bioprosthetic conduits comprising animal ureters have been proposed, but it has now been shown, by careful examination of such ureters, that prior to the customary fixation or tanning treatment, the inner epithelial surface of the ureter is liable to fragmentation, giving rise to the possibility of fluid flow disruption and consequent emboli formation.

Thus, the present invention provides a method of preparing a bioprosthetic conduit comprising an animal ureter, including the steps: (1) distending the ureter sufficient to expand the internal surface thereof to give a substantially smooth surface, and (2) subjecting the ureter while in a distended condition to a fixation treatment.

The method may also include the step of substantially removing the inner epithelial surface of the ureter.

The present invention also provides (1) an animal ureter suitable for use as a bioprosthetic conduit which has had the inner epithelial surface thereof substantially removed, and (2) a bioprosthetic conduit comprising an animal ureter which has had the inner epithelial surface thereof substantially removed and 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 ureter with glycerol.

Desirably, the treatment takes place following the removal of the inner epithelial surface and prior to the distension and fixing of the ureter.

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 ureters are kept in a moist condition during the practice of the invention in an isotonic potassium based buffer solution of pH 7.4 free of sodium. This is to ensure that the muscle fibres of the ureters are maintained in a loose, flaccid state to permit subsequent full distension thereof.

The removal or disruption of the inner epithelial surface of the ureter may be carried out by mechanical, enzymatic or chelating treatments or a combination of such treatments.

Removal of the epithelial surface tends to provides a less smooth remaining surface, but one which is less susceptible to fragmentation.

Mechanical Treatment. The ureter is everted and the exposed inner epithelial surface is rubbed away with a rough scouring cloth.

After removal of the epithelial surface the ureter is re-everted.

Enzymatic Treatment. The distended inner epithelial surface is removed by treatment with a 0.1 to 1% trypsin solution at pH 8.4 for up to 4 periods of 30 minutes each at 37"C (without external recirculation).

Chelating Treatment. (Optional). The distended inner epithelial surface is removed by treatment with a 200 mg/litre solution of ethylene diamine tetra acetic acid for 30 minutes at 37"C (without external recirculation).

The above removal treatments may be applied singly or in any combination or order.

Each treatment is followed by thorough flushing with isotonic potassium phosphate buffer until the effluent is clear and of the correct pH. Only then is recirculation and the fixation treatment commenced.

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. Preferably the ureter is distended by the use of fluid pressure, but other methods of distension, such as mechanical methods, may be employed.

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

Freshly removed pig ureters are stripped of exterior fat and thoroughly washed through with isotonic potassium phosphate based buffer at 4"C.

Each ureter is held horizontal, straight and untwisted between two mounting cannulae which can be adjusted for length, tension and twist. The ureters are flushed through, optionally with glycerol, and left immersed therein for 7 days. The glycerol is then washed from the ureters using an isotonic potassium based buffer solution of pH 7.4 free of sodium.

Thereafter, the mounted ureters are submerged in a bath of the same buffer solution and the solution circulated from a pressure head of 50 mm mercury through the ureters, discharging from the distal cannula at an adjustable pressure head of between 200 and 400 mm water. Under a pressure of 50 mm mercury the ureter wall is distended and the ureter opened to provide a continuous hole therethrough. Such distension has the effect of substantially removing any internal surface convolutions of the ureter to provide a substantially smooth internal surface. Buffer pressure is maintained by recirculation of the overflow via a pressure head reservoir.When several ureters have been assembled under pressure, the whole buffer volume is charged with concentrated gluteraldehyde solution to a final concentration of 0.2%, and the distended ureters are allowed to fix therein for at least 18 hours, during which time the gluteraldehyde solution remains 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 method of preparing a bioprosthetic conduit comprising an animal ureter, including the steps: (1) distending the ureter sufficient to expand the internal surface thereof to give a substantially smooth surface, and (2) subjecting the ureter while in a distended condition to a fixation treatment.

2. A method as claimed in Claim 1 in which a non-human ureter is used.

3. A method as claimed in Claim 2 in which a pig ureter is used.

4. A method as claimed in any of one of Claims 1 to 3 including the step of substantially removing the inner epithelial surface of the ureter.

5. A method as claimed in Claim 4 in which the inner epithelial surface is removed by a mechanical treatment.

6. A method as claimed in Claim 4 in which the inner epithelial surface is removed by an enzymatic treatment.

7. A method as claimed in Claim 4 in which the inner epithelial surface is removed by a chelating treatment.

8. A method according to Claim 4 in which the inner epithelial surface is removed by a combination of two or more of the treatments claimed in Claims 5 to 7.

9. A method as claimed in any one of the preceding claims in which prior to distension the ureter is treated with glycerol.

10. A method as claimed in any one of the preceding claims in which the ureter is distended by fluid pressure.

11. A method as claimed in any of the preceding claims in which the distended ureter is subjected to fixation by a gluteraldehyde solution.

12. A method as claimed in any one of the preceding claims in which the ureter is kept in a moist condition in an isotonic potassium based buffer solution free of sodium.

13. An animal ureter suitable for use as a bioprosthetic conduit which has had the inner epithelial surface thereof substantially removed.

14. A bioprosthetic conduit comprising an animal ureter which has had the inner epithelial surface thereof substantially removed and 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.

15. A conduit as claimed in Claim 14 comprising a non-human ureter.

16. A conduit as claimed in Claim 15 comprising a pig ureter.

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

18. An animal ureter suitable for use as a biporosthetic conduit substantially as hereinbe fore described with reference to the Example of the invention.

19. A bioprosthetic conduit substantially as hereinbefore described with reference to the Example of the invention.