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Abstract

The accumulation of intracellular calcium ([Ca2+]i) caused by ischemia-reperfusion during liver transplantation has been implicated as a factor leading to primary graft nonfunction. Plasma membrane (PM) and endoplasmic reticulum (ER) Ca2+-adenosinetriphosphatases (ATPases) are the primary transporters that maintain [Ca2+]i homeostasis in the liver. We hypothesized that the porcine liver is better than the rat liver as a model for the study of human liver Ca2+-ATPase activity. We also hypothesized that cold preservation would depress Ca2+-ATPase activity in the porcine liver. Pig and rat livers were harvested, and human liver samples were obtained from surgical resection specimens. All were preserved with University of Wisconsin solution, and porcine livers were also preserved on ice for 2 to 18 hours. Ca2+-ATPase activity was measured after incubation with 45Ca2+ and adenosine triphosphate in the presence of specific Ca2+-ATPase inhibitors. Porcine PM and ER Ca2+-ATPase activities were 0.47 ± 0.03 and 1.57 ± 0.10 nmol of Ca2+/mg of protein/min, respectively. This was not significantly different from human liver, whereas rat liver was significantly greater at 2.60 ± 0.03 and 9.2 ± 0.9 nmol of Ca2+/mg of protein/min, respectively. We conclude that the Ca2+-ATPase activity in the pig liver is equivalent to that of human liver, and thus, the pig liver is a better model than the rat liver. Cold preservation studies showed a significant decrease in porcine hepatic PM Ca2+-ATPase activity after 4 hours of storage and near-total inhibition after 12 hours. Porcine hepatic ER Ca2+-ATPase activity showed a 45% decrease in activity by 12 hours and a 69% decrease by 18 hours. We conclude that cold ischemia at clinically relevant times depresses PM Ca2+-ATPase more than ER Ca2+-ATPase activity in pig liver homogenates.