ROLE OF EXOGENOUS L-ARGININE IN HEPATIC ISCHEMIA-REPERFUSION INJURY

Plasma L-arginine is usually deficient immediately after hepatic reper fusion in orthotopic liver transplantation, which may also contribute to the occurrence of either hepatic ischemia-reperfusion injury or pul monary hypertension. In this study, exogenous L-arginine was thus expe rimentally used to reverse the deficient status of the L-arginine/NO p athway. An in vivo model of I hr hepatic ischemia and reperfusion was thus tested in both rats (Experiment A) and pigs (Experiment B). In Ex periment A, 10 mg/kg of L-arginine (group 1, n = 7), D-arginine (group 2, n = 7), or saline (group 3, n = 7) was administered through the po rtal vein, The hepatic tissue blood flow, at 20 min after reperfusion, improved in group 1 (70.7 +/- 7.0% of the preclamp levels) compared t o groups 2 and 3. The serum glutamate oxaloacetate transaminase levels at 24 hr after reperfusion were also lower in group 1 (320 +/- 22.2 I U/L) than in either group 2 or group 3, The intrahepatic NO levels sho wed a temporal burst (>15,000 pA current) after reperfusion only in gr oup 1, In Experiment B, 10 mg/kg of L-arginine (group 4, n = 5), D-arg inine (group 5, n = 5), or 10 mi of saline (group 6, n = 5) was admini stered through the portal vein, In group 4, the MPAP (mean pulmonary a rterial pressure)/MAP (mean arterial pressure) was lower than that obs erved in groups 5 and 6. In conclusion, exogenous L-arginine administe red from the portal vein was thus found to be effective in mitigating both portal hypertension and reperfusion injury by producing an increa sed amount of NO immediately after reperfusion. (C) 1997 Academic Pres s.