Effects of amrinone on hepatic ischemia-reperfusion injury in rats.
OBJECTIVE
The present study was designed to investigate the effect of amrinone, a phosphodiesterase III inhibitor, on hepatic ischemia-reperfusion injury in rats.


METHODS
Amrinone was infused at a rate of 20 or 100 microg/kg/min, and 60-min partial ischemia was induced. The effects of amrinone on hemodynamic status, hepatic tissue cyclic adenosine 5'-monophosphate (cAMP), hepatic tissue blood flow, platelet aggregation and plasma levels of transaminase were examined. The expression of intercellular adhesion molecule-1 (ICAM-1) and myeloperoxidase activity were analyzed and histological examination was performed in the injured liver. The cumulative survival rates for 14 days were also examined.


RESULTS
Hemodynamic status was not affected by amrinone. The levels of cAMP during reperfusion were significantly higher in rats with amrinone. Hepatic tissue blood flow during reperfusion was increased and platelet aggregation was inhibited by amrinone. The expression of ICAM-1 mRNA and protein in the injured liver was suppressed in rats with amrinone. The levels of transaminase, necrotic changes and myeloperoxidase activity were suppressed after reperfusion and higher survival was achieved in the rats treated with amrinone.


CONCLUSIONS
Amrinone protected against ischemia-reperfusion injury of the liver in the present model.
Kobayashi
Takashi
T
Hepato-Biliary-Pancreatic Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Sugawara
Yasuhiko
Y
Ohkubo
Takao
T
Imamura
Hiroshi
H
Makuuchi
Masatoshi
M
D000410:Alanine Transaminase / Q000378:metabolism; D000676:Amrinone / Q000494:pharmacology*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D008102:Liver Circulation / Q000187:drug effects; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D015996:Survival Rate
D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D000242:Cyclic AMP; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000676:Amrinone