Transplants
The present invention relates to a method of reducing injury to cells, a tissue or organ to be explanted from a body and upon implantation into a body by administering a composition to the cell, tissue or organ, including: (i) a potassium channel opener or agonist and/or an adenosine receptor agonist; and (ii) an antiarrhythmic agent. The invention also provides a composition for reducing injury to vasculature ex vivo including: (i) a potassium channel opener or agonist and/or an adenosine receptor agonist; and (ii) an antiarrhythmic agent.
1. A method of reducing the patency failure rate of a transplanted vasculature graft, the method comprising:
Prior to transplantation, administering ex vivo to the graft a composition comprising
i) a potassium channel opener or agonist and/or an adenosine receptor agonist; and
ii) an anti-arrhythmic agent
wherein the patency failure rate post operatively of the transplanted vasculature graft is reduced.
2. A method according to claim 1 , wherein the composition further includes at least one muscle relaxant.
3. A method according to claim 2 , wherein the muscle relaxant is selected from the group consisting of a botulinum toxin, myosin light chain kinase inhibitor, calmodulin blocker, calcium channel blocker, nitric oxide donor, dipyridamole, beta blocker, Na/H inhibitor, high magnesium, opioid, phosphodiesterase inhibitors, alpha-adrenergic receptor antagonists and Rho kinase inhibitors.
4. A method according to claim 3 , wherein the phosphodiesterase inhibitor is selected from the group consisting of papaverine, milrinone, theophylline and dipyridamole.
5. A method according to claim 3 , wherein the alpha-adrenergic receptor antagonist is phenoxybenzamine.
6. A method according to claim 3 , wherein the Rho kinase inhibitor is selected from the group consisting of HA1077 and fausdil.
7. A method according to claim 1 , wherein the composition is pre-mixed with the patient's blood.
8. A method according to claim 1 , wherein the vasculature is a blood vessel, or a denuded vasculature ring.
9. A method according to claim 8 , wherein the blood vessel is a saphenous vein.
10. A method according to claim 1 , wherein the composition is administered to the vascular graft during harvesting, storage pending implantation and pressure testing.
11. A method according to claim 1 , wherein the composition is administered to the vasculature graft, optionally with at least one smooth muscle relaxant, upon implantation and/or recovery of the vasculature.
12. A method according to claim 1 , wherein the composition is also administered systemically or at the site of surgery to the vasculature prior to surgery.
13. A method according to claim 12 , wherein the composition is administered as a non-arresting bolus injection or delivered continuously via an intravenous drip.
14. A method according to claim 1 , wherein the ex vivo vasculature graft is maintained in a bath of, or having a continuous supply of, the composition.
15. A method according to claim 1 , wherein the potassium channel opener or agonist and/or an adenosine receptor agonist is adenosine.
16. A method according to claim 1 , wherein the anti-arrhythmic agent is lignocaine.
17. A method according to claim 1 , wherein the potassium channel opener or agonist and/or an adenosine receptor agonist is adenosine and the anti-arrhythmic agent is lignocaine.