FK506 maintains cellular calcium homeostasis in ischemia-reperfusion injury of the canine liver.

Increased morbidity and mortality following transplantation surgery due to the primary nonfunction and dysfunction of the liver poses a great challenge and has increased the crescendo of research work in this field. In this study, we have tried to address the issue concerning the changes in Ca2+ homeostasis and hepatic microcirculation in 90 min of ischemia followed by reperfusion of the liver after FK506 pretreatment. Twenty dogs divided into two groups; group I (0.15 mg/kg/day FK506 for 3 days, im) and group II (control) were used for the measurement of mitochondrial (mit) and total cellular Ca2+ by atomic absorption spectrophotometer and hepatic microcirculation with laser Doppler flowmeter. Serum AST leakage was significantly (P < 0.05) suppressed in group I at 6 hr after reperfusion. The percentage gain in mit Ca2+ in group I was significantly (P < 0.05) inhibited compared to that in group II at 15 min after reperfusion and also when compared with the preischemic value it was significantly (P < 0.05) elevated at 30 min after reperfusion in group II only. FK pretreatment significantly (P < 0.05) inhibited the overload in total cellular Ca2+ at 15 and 30 min after reperfusion. Moreover, hepatic microcirculation was significantly (P < 0.001) better in group I between 2 and 6 hr after reperfusion. In conclusion, the ameliorating property of FK in ischemia-reperfusion may be explained by prevention of the cellular Ca2+ overload during the perireperfusion period.