Organ and biological tissue preservation cold storage solution

Abstract

Cold storage solutions for the preservation of organs and biological tissues prior to implantation, including a cellular energy production stimulator under anaerobic conditions, an anti-inflammatory agent, and an oxygen free radical scavenger.

Description

REFERENCE TO RELATED APPLICATION[0001] This application claims the benefit of U.S. Provisional Application No. 60 / 240,023 filed on Oct. 13, 2000, entitled "Organ and Biological Tissue Preservation Cold Storage Solution," which is incorporated herein by reference.[0002] The invention relates to the field of organ and biological tissue preservation. In particular, the invention relates to cold storage solutions for the preservation of organs and biological tissues for implant.BACKGROUND OF INVENTION[0003] It is believed that the ability to preserve human organs for a few days by cold storage after initial flushing with an intracellular electrolyte solution or by pulsatile perfusion with an electrolyte-protein solution has allowed sufficient time for histo-compatibility testing of donor and recipient. It is also believed that preservation by solution or perfusion has also allowed for organ sharing among transplant centers, careful preoperative preparation of the recipient, time for pre...

AI Technical Summary

Benefits of technology

[0015] A cold storage solution of the invention also includes an anti-inflammatory agent. Dexamethasone, which is a steroid analogue, is used for its anti-inflammatory properties. Dexamethasone has a prolonged plasma half-life and pronounced growth-suppressing properties.

[0016] A cold storage solution of the invention also contains an oxygen free radical scavenger. One example, superoxide dismutase, is known for its potent free oxygen radical scavenging properties. Preferably, the superoxide dismutase is conjugated to polyethylene glycol so that its half-life is extended by a factor of about 100 times. Superoxide dismutase is a potent scavenger of several classes of free oxygen radicals during cold ischemia and upon reperfusion. When conjugated to polyethylene glycol, superoxide dismutase can remain active for several hours in the cold storage solution of the invention.

[0017] According to a preferred embodiment of the invention, an organ and biological tissue preservation cold storage solution containing superoxide dismutase in the preserving solution significantly improves vascular resistance, vascular flow, and calcium efflux during the organ preservation period. The inhibition of calcium efflux over time in kidneys preserved by the proposed solution suggests that, in addition to vasoactive effects, an additional cytoprotective and cryoprotective effect may also be important in ameliorating ischemic injury. These improvements are substantiated ultrastructurally by improved appearance of mitochondria in proximal tubular cells compared to mitochondria from kidneys not exposed to the proposed solution.

Problems solved by technology

An obstacle that may arise in the effort to increase utilization is that maximal utilization may require transplantation of all available organs, including extended criteria donor organs.

However, by extending the criteria for suitability of donor organs, transplant clinicians may risk a penalty with respect to graft function, diminishing the efficiency of organ utilization if transplanted organs exhibit inferior graft survival.

The mechanisms of injuries sustained by the cadaveric renal allograft during pre-preservation, cold ischemic preservation and reperfusion are believed to be complex and not fully understood.

Hypothermically-induced injury to the endothelium during preservation may lead to drastic alterations in cytoskeletal and organelle structures.

Hypothermic preservation may disrupt the membrane electrical potential gradient, resulting in ion redistribution and uncontrolled circulation of Ca++.

The depletion of ATP stored during I / R may compromise ATP-dependent pumps that extrude Ca++ from the cell and the energy intensive shuttle of organelle membranes, causing a dramatic elevation of intracellular free Ca++.

Alterations in cytosolic Ca++ concentration may disrupt several intracellular functions, many of which may result in damaging effects.