Interspecies differences in hepatic Ca2+-ATPase activity and the effect ofcold preservation on porcine liver Ca2+-ATPase function

The accumulation of intracellular calcium ([Ca2+](i)) caused by ischemia-re perfusion during liver transplantation has been implicated as a factor lead ing to primary graft nonfunction. Plasma membrane (PM) and endoplasmic reti culum (ER) Ca2+-adenosinetriphosphatases (ATPases) are the primary transpor ters 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 Ca2+-pothesized that cold preser vation 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 solut ion, and porcine livers were also preserved on ice for 2 to 18 hours. Ca2+- ATPase activity was measured after incubation with Ca-45(2+) 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 differen t 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 conc lude 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 live r. Cold preservation studies showed a significant decrease in porcine hepat ic PM Ca2+-ATPase activity after 4 hours of storage and near-total inhibiti on after 12 hours. Porcine hepatic ER Ca2+-ATPase activity showed a 45% dec rease 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 mo re than ER Ca2+-ATPase activity in pig liver homogenates.