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

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 with⁴⁵Ca²⁺ 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.