Protective effect of diltiazem on hepatic ischemia-reperfusion injury in rats by improving liver tissue blood flow.
BACKGROUND
Cytosolic calcium ions are known to play an important role in ischemia-reperfusion (IR) injury. However, the protective effect of calcium channel blockers remains controversial in liver IR injury. Moreover, calcium channel blockers improve hepatic IR injury not due to blocking an increase in hepatic calcium concentration. Therefore, we hypothesized that calcium antagonists protected a liver from IR injury by a vasodilatory action rather than by the inhibition of an increase in Ca2+ within parenchymal cells. This study evaluated the effects of diltiazem, a calcium channel blocker, on liver energy metabolism and blood flow after IR injury.


METHODS
Twenty-seven rats underwent hepatic ischemia for 30 minutes followed by 60 minutes of reperfusion. The animals were allocated into group C (without drug); group D5 (diltiazem, 5 microg/kg per min); or group D10 (diltiazem, 10 microg/kg per min). Diltiazem was infused before laparotomy and then throughout the experiment.


RESULTS
After 60 minutes of reperfusion, liver tissue blood flow and ATP concentrations were significantly higher in group D10 than the other animals (both, P < .05). Changes in ATP values strongly correlated those observed in blood flow (R = 0.80, P < .001).


CONCLUSIONS
Diltiazem improved ATP-generating capacity during reperfusion by improving liver tissue blood flow. An improvement in hepatic tissue perfusion may be a therapeutic strategy for liver IR injury.
Chin
S
S
Department of Surgery II, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan. chin8ito@ybb.ne.jp
Ikeda
M
M
Ozaki
M
M
Kameoka
S
S
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology*; D004195:Disease Models, Animal; D008099:Liver / Q000098:blood supply*; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D004110:Diltiazem