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 r...

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Published in:The Journal of surgical research Vol. 69; no. 2; pp. 429 - 434
Main Authors: SHIRAISHI, M, HIROYASU, S, NAGAHAMA, M, MIYAGUNI, T, HIGA, T, TOMORI, H, OKUHAMA, Y, KUSANO, T, MUTO, Y
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Published: New York, NY Elsevier 01-05-1997
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Abstract 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.
AbstractList 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.
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.
Author MUTO, Y
TOMORI, H
MIYAGUNI, T
KUSANO, T
HIGA, T
HIROYASU, S
NAGAHAMA, M
SHIRAISHI, M
OKUHAMA, Y
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Issue 2
Keywords Replacement therapy
Pathophysiology
Rat
Liver
Rodentia
Cardiovascular disease
Hepatic disease
Experimental study
Vascular disease
Vertebrata
Mammalia
Reperfusion
Arginine
Ischemia
Animal
Nitric oxide
Digestive diseases
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StartPage 429
SubjectTerms Animals
Arginine - pharmacology
Aspartate Aminotransferases - metabolism
Biological and medical sciences
Blood Pressure
Citrulline - blood
Cyclic GMP - blood
Female
Gastroenterology. Liver. Pancreas. Abdomen
Hemodynamics
Liver - blood supply
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
Nitrates - metabolism
Nitric Oxide - metabolism
Nitrites - metabolism
Other diseases. Semiology
Rats
Rats, Wistar
Reperfusion Injury - etiology
Swine
Time Factors
Title Role of exogenous L-arginine in hepatic ischemia-reperfusion injury
URI https://www.ncbi.nlm.nih.gov/pubmed/9224419
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Volume 69
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