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.
Dhar
D K
DK
Second Department of Surgery, Shimane Medical University, Izumo, Japan.
Takemoto
Y
Y
Nagasue
N
N
Uchida
M
M
Ono
T
T
Nakamura
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007511:Ischemia / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008102:Liver Circulation; D008297:Male; D008833:Microcirculation; D015427:Reperfusion Injury / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D002118:Calcium; D016559:Tacrolimus