Role of exogenous L-arginine in hepatic ischemia-reperfusion injury.
Plasma L-arginine is usually deficient immediately after hepatic reperfusion in orthotopic liver transplantation, which may also contribute to the occurrence of either hepatic ischemia-reperfusion injury or pulmonary hypertension. In this study, exogenous L-arginine was thus experimentally used to reverse the deficient status of the L-arginine/NO pathway. An in vivo model of 1 hr hepatic ischemia and reperfusion was thus tested in both rats (Experiment A) and pigs (Experiment B). In Experiment 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 portal vein. The hepatic tissue blood flow, at 20 min after reperfusion, improved in group 1 (70.7 +/- 7.0% of the preclamp levels) compared to groups 2 and 3. The serum glutamate oxaloacetate transaminase levels at 24 hr after reperfusion were also lower in group 1 (320 +/- 22.2 IU/L) than in either group 2 or group 3. The intrahepatic NO levels showed a temporal burst (> 15,000 pA current) after reperfusion only in group 1. In Experiment B, 10 mg/kg of L-arginine (group 4, n = 5), D-arginine (group 5, n = 5), or 10 ml of saline (group 6, n = 5) was administered through the portal vein. In group 4, the MPAP (mean pulmonary arterial pressure)/MAP (mean arterial pressure) was lower than that observed in groups 5 and 6. In conclusion, exogenous L-arginine administered from the portal vein was thus found to be effective in mitigating both portal hypertension and reperfusion injury by producing an increased amount of NO immediately after reperfusion.
Shiraishi
M
M
First Department of Surgery, University of Ryukyu, School of Medicine, Okinawa, Japan.
Hiroyasu
S
S
Nagahama
M
M
Miyaguni
T
T
Higa
T
T
Tomori
H
H
Okuhama
Y
Y
Kusano
T
T
Muto
Y
Y
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001794:Blood Pressure; D002956:Citrulline / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D005260:Female; D006439:Hemodynamics; D008099:Liver / Q000098:blood supply*; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology*; D013552:Swine; D013997:Time Factors
D009566:Nitrates; D009573:Nitrites; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D001219:Aspartate Aminotransferases; D006152:Cyclic GMP