Machine perfusion solution for organ and biological tissue preservation
View Patent ↗Machine perfusion solutions for the presentation of organs and biological tissues prior to implantation, including a prostaglandin having vasodilatory, membrane stabilizing, platelet aggregation prevention upon reperfusion, and complement activation inhibitory properties, a nitric oxide donor, a glutathione-forming agent, and an oxygen free radical scavenger.
1. The machine perfusion solution of claim 1 wherein the solution comprises about 1,000 micrograms/L prostaglandin E1, about 10 mg/L nitroglycerin, and about 0.2 mg/L N-acetylcysteine, further comprising:
about 60–100 mM sodium gluconate;
about 20–30 mM KH 2 PO 4 ;
about 3–8 mM magnesium gluconate;
about 3–8 mM adenine;
about 3–8 mM ribose;
about 0.3–0.8 mM CaCl 2 ;
about 8–15 mM HEPES;
about 8–15 mM glucose;
about 15–50 mM mannitol; and
about 45–55 g/L pentastarch.
2. The machine perfusion solution of claim 1 wherein the solution comprises about 1,000 micrograms/L prostaglandin E1, about 10 mg/L nitroglycerin, and about 0.2 mg/L N-acetylcysteine, further comprising:
about 80 mM sodium gluconate;
about 25 mM KH 2 PO 4 ;
about 5 mM magnesium gluconate;
about 5 mM adenine;
about 5 mM ribose;
about 0.5 mM CaCl 2 ;
about 10 mM HEPES;
about 10 mM glucose;
about 30 mM mannitol; and
about 50 g/L pentastarch.
3. The machine perfusion solution of claim 1 or 2 further comprising at least one of distilled water and deionized water.
4. An organ or biological tissue preservation aqueous machine perfusion solution comprising:
about 1,000 micrograms/L prostaglandin E1;
about 10 mg/L nitroglycerin;
about 0.2 mg/L N-acetylcysteine;
about 40–160 mM sodium gluconate;
about 10–50 mM KH 2 PO 4 ;
about 1–15 mM magnesium gluconate;
about 1–15 mM adenine;
about 1–15 mM ribose;
about 0.1–2 mM CaCl 2 ;
about 1–30 mM HEPES;
about 1–30 mM glucose;
about 10–100 mM mannitol;
about 40–60 g/L pentastarch; and
about 700–900 mL sterile water.
5. A method for preserving a cadaveric organ or biological tissue, wherein the organ or tissue is a kidney or tissue from a kidney, comprising:
pouring the machine perfusion solution of claim 1 , 2 , 3 or 4 into a chamber that mimics at least one of a deep hypothermic environment and physiological environment;
circulating the machine perfusion solution continuously through the chamber;
inserting the at least one of a cadaveric organ and tissue into the chamber; and
flushing the at least one of a cadaveric organ and tissue with the machine perfusion solution.
6. The method of claim 5 wherein the flushing comprises:
infusing the solution through vasculature of the at least one of a cadaveric organ and tissue.
7. The method of claim 5 wherein the flushing comprises:
infusing the solution over or through an avascular biological substance of the at least one of a cadaveric organ and tissue to maintain viability during an ex vivo period.
8. The method of claim 5 further comprising:
monitoring parameters of the at least one of a cadaveric organ and tissue.
9. The method of claim 5 further comprising:
exsanguinating the at least one of a cadaveric organ and tissue; and
replacing the machine perfusion solution with at least blood to return the at least one of a cadaveric organ and tissue to a normothermic condition.
10. A method of preparing an organ or biological tissue preservation machine perfusion solution of claim 1 , 2 , 3 or 4 comprising:
providing a solution with sterile water;
adding the sodium gluconate, potassium phosphate, adenine, ribose, calcium chloride, pentastarch, magnesium gluconate, HEPES, glucose, mannitol, and insulin to the solution; and
mixing the prostaglandin E1, nitroglycerin and N-acetylcysteine into the solution.
11. The method of claim 10 further comprising:
mixing the solution until all components are dissolved.
12. The method of claim 10 further comprising:
infusing the pentastarch under pressure through a dialyzing filter;
centrifuging the prostaglandin E1 under hypothermic conditions; and
filtering the centrifuged prostaglandin E1.