Pharmacological modification to prevent reperfusion injury following liver transplantation

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Cohen, Ari J.
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The principal objectives of this were to determine whether hepatocyte membrane potentials (PD) are altered during liver transplantation and whether such changes may be of pathophysiologic importance in ischemia/reperfusion injury and graft survival. Livers of adult male Sprague-Dawley rats (N = 3-4/group) were impaled with intracellular microelectrodes prior to and at various time periods for six hours following complete hepatic resection. Just prior to resection each liver was perfused with preservation solutions associated with high (normal saline, NS), moderate (Eurocollins, EC) and low (University of Wisconsin solution, UW) risks of reperfusion injury. To determine whether changes are of pathophysiologic importance, the NS solution was modified (addition of 0.1% ethanol) to achieve similar PD changes as those observed with UW. Liver transplants were then performed using a nonarterialized, cuff technique in adult Lewis rats where the donor livers had been perfused and preserved for six hours with e ther NS or the modified NS, (MNS) solution. Regarding the effects of PD changes on ionic flux, intracellular calcium levels were documented by fluorescence video microscopy using Fura-2 in isolated hepatocytes exposed to NS, UW and MNS solutions. (Abstract shortened by UMI.)