Effect of verapamil on hepatic reperfusion injury after prolonged ischemia in pigs.
This study investigated the effect of verapamil on prolonged and severe ischemic injury and elucidated the association of the calcium blocking action with cellular injury, assessing changes in hepatic calcium concentrations during ischemia and reperfusion in pigs. Hepatic ischemia was produced for 180 min by clamping both the hepatic artery and portal vein during temporary portacaval shunt performed before the induction of ischemia. Pigs were divided into two groups: the animals in the verapamil group (Group V, n = 6) received continuous administration of 0.025 mg/kg per min of verapamil intraportally for 20 min before ischemia. The control group (Group C) received nothing. A better survival rate was observed in Group V than in Group C (p < 0.01), but serum aspartate aminotransferase was higher in Group V after reperfusion (p < 0.05). There were no significant changes in hepatic calcium concentrations during ischemia in either group, but it increased immediately after reperfusion in both groups. However, no significant difference was found between the two groups. Recovery of the pyruvate/lactate ratio in Group V tended to be better after reperfusion compared to Group C (p = 0.08). These data suggest that the pre-ischemic administration of verapamil produced better survival in animals after prolonged normothermic ischemia. However, the reperfused liver suffered more severe damage in the first 6 h after reperfusion in the verapamil-treated animals. Moreover, there seemed to be very little blocking action of calcium influx. A reduced oxygen requirement may be involved in the protective action of verapamil on animal survival.
Uchida
M
M
Second Department of Surgery, Shimane Medical University, Izumo, Japan.
Takemoto
Y
Y
Nagasue
N
N
Dhar
D K
DK
Kohno
H
H
Nakamura
T
T
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010100:Oxygen / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D013552:Swine / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014700:Verapamil; D001219:Aspartate Aminotransferases; D010100:Oxygen; D002118:Calcium