Role of platelets in hepatic allograft preservation injury in the rat.
Cold preservation of liver allografts injuries hepatic sinusoidal lining cells. This injury is exacerbated on reperfusion, in part because of adhesion of leukocytes. Platelets also adhere to activated endothelial surfaces. In this study we examined the role of platelets in preservation injury. Our specific aim was to determine whether the degree of platelet adhesion on reperfusion of preserved rat livers was related to duration of cold or warm ischemia and whether platelet adhesion resulted in injury to allografts. We also examined the effect of prior activation of platelets on adhesion and injury. Rat livers were preserved at 1 degree C for different time periods in University of Wisconsin solution and then reperfused for 3 hr on the isolated perfused rat liver system with Krebs-Henseleit solution to which unactivated isolated rat platelets were added. Other livers were rewarmed before reperfusion or reperfused with activated platelets. Platelets were lost from the circulation in all studies; the percentage reduction of circulating platelets was dependent on the length of preservation. The initial platelet concentration did not affect the rate of reduction of platelets in the circuit. Rewarming before reperfusion increased platelet adherence, and prior activation also increased adherence. With electron microscopy we determined that platelets adhered in small aggregates to endothelial cells or endothelial cell remnants. Adherent platelets appeared more activated and contained fewer granules than did unperfused platelets. Liver injury as measured by release of transaminases into perfusate was worsened by longer periods of cold preservation and by addition of rewarming to the protocol. The presence of platelets under these circumstances aggravated injury. Prior activation of platelets also increased the extent of injury. These studies show that platelets have an important role in cold preservation-reperfusion injury.
Cywes
R
R
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Department of Biochemistry, Toronto, Ontario, Canada.
Packham
M A
MA
Tietze
L
L
Sanabria
J R
JR
Harvey
P R
PR
Phillips
M J
MJ
Strasberg
S M
SM
D000410:Alanine Transaminase / Q000032:analysis; D000818:Animals; D001219:Aspartate Aminotransferases / Q000032:analysis; D001792:Blood Platelets / Q000502:physiology*; D003080:Cold Temperature; D006358:Hot Temperature; D007511:Ischemia; D008099:Liver / Q000648:ultrastructure; D016031:Liver Transplantation; D008297:Male; D008854:Microscopy, Electron; D009926:Organ Preservation / Q000379:methods*; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D015427:Reperfusion Injury / Q000517:prevention & control*; D013997:Time Factors; D014184:Transplantation, Homologous
D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase