LONGTERM ORGAN PRESERVATION FOR TRANSPLANTATION

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The objective of this study is to develop a safe and reliable technique for long-term organ preservation for transplantation. Organ transplantations have proved successful in the treatment of patients with end-stage organ failure. Application of these procedures is severely Limited by the lack of suitable donor organs. Safe preservation time for the heart and lungs Is still limited to 4-6 hours. Methods with such a short period of time have three main disadvantages: (1) It limits the geographic area from which to obtain grafts. (2) It limits the tame for histocompatibility tests and (3) It raises the possibility of inadequate tissue protection. Advancements in preservation techniques for vital organs such as the heart, lungs and liver are extremely important since alternative methods of long-term artificial support do not exist. We have developed and studied a new autoperfusion technique for long-term organ preservation. With the animals are anesthetized and artificially ventilated, the heart, lungs, liver, pancreas, duodenum and both kidneys are removed en bloc while being perfused by the heart and oxygenated by the lungs. A respirator is used for ventilation. Fresh blood, electrolytes, antibiotics and nutrients are infused by intravenous drip. No anticoagulants or inotropic drugs are necessary. This is a self- contained and self-adjusted system and requires very little intervention. The heart pumps blood to all the organs. The lungs oxygenate the blood. The liver maintains its biological functions. Electrolyte and water balances are maintained and metabolic wastes are removed by the kidneys. This preparation preserves the natural anatomic connections of the organs without assistance of foreign material, and the energy and substrate exchanges between organs are preserved. In a pilot study, the survival tame ranged from 41 to 60 hours with stable hemodynamics and organ function. In this proposal, we intend to study the relationship between platelet aggregation and tissue survival time; study the relationship between substrate uptake and organ function; study organ function and survival time under different temperature settings; transplant the heart after 24 hours of preservation; and transplant the heart after 12-24 hours of autoperfusion preservation plus 4-6 hours of hypothermic storage. Similar studies have not been done before. These studies will gain new knowledge of ex vivo organ function and survival during long-term autoperfusion and provide further evaluation for possible clinical application of this technique.