Dipyridamole protects the liver against warm ischemia and reperfusion injury.
BACKGROUND
Adenosine, a metabolite of adenosine triphosphate degradation during ischemia, is reported to attenuate ischemia and reperfusion injury in several tissues. Dipyridamole is a nucleoside transport inhibitor that augments endogenous adenosine. In this study, we tested whether dipyridamole would attenuate hepatic I/R injury. For this purpose, dipyridamole was applied to a 2-hour total hepatic vascular exclusion model in dogs.


METHODS
Dipyridamole (DYP) was given by continuous intravenous infusion for 1 hour before ischemia at a dose of 0.25 mg/kg (high-DYP, n = 6), 0.1 mg/kg (medium-DYP, n = 6), or 0.05 mg/kg (low-DYP, n = 6). Nontreated animals were used as ischemic controls (CT, n = 12). Two-week survival, systemic and hepatic hemodynamics, liver function tests, energy metabolism, adenosine 3', 5'-cyclic monophosphate (cyclic AMP) levels, platelet numbers, arachidonic acid metabolites, and histopathology were analyzed.


RESULTS
Two-week animal survival was 25% in CT, 17% in high-DYP, 100% in medium-DYP, and 17% in low-DYP. Dipyridamole significantly improved postreperfusion hepatic blood flow and energy metabolism, attenuated liver enzyme release and purine catabolite production, and augmented cyclic AMP levels. The medium dose of dipyridamole lessened platelet aggregation, thromboxane B2 production, and polymorphonuclear neutrophil infiltration, and improved survival.


CONCLUSIONS
We demonstrated marked hepatoprotective effects of dipyridamole against severe ischemia and reperfusion injury in canine livers. Dipyridamole is a promising agent for liver surgery and transplantation.
Taniguchi
Masahiko
M
First Department of Surgery, Hokkaido University School of Medicine, N-15 W-7 Kita-ku, Sapporo 060-8638, Japan.
Magata
Shinichirou
S
Suzuki
Tomomi
T
Shimamura
Tsuyoshi
T
Jin
Maeng Bong
MB
Iida
Junichi
J
Furukawa
Hiroyuki
H
Todo
Satoru
S
D000818:Animals; D001794:Blood Pressure; D000242:Cyclic AMP / Q000378:metabolism; D004176:Dipyridamole / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004285:Dogs; D004734:Energy Metabolism; D005260:Female; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008102:Liver Circulation; D033703:Nucleoside Transport Proteins / Q000037:antagonists & inhibitors*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
D033703:Nucleoside Transport Proteins; D010726:Phosphodiesterase Inhibitors; D004176:Dipyridamole; D000242:Cyclic AMP