The protective effects of L-arginine after liver ischaemia/reperfusion injury in a pig model.
Hepatic ischaemia/reperfusion is characterized by circulatory and metabolic derangement, liver dysfunction, and tissue damage. To evaluate the role of L-arginine, a substrate of nitric oxide, in ischaemia/reperfusion injury, total liver ischaemia was induced for 120 min in 22 Landrace x Large White female pigs, which were randomly assigned to a treatment group (10 animals) or a control group (12 animals). An L-arginine bolus (540 mg/kg i.v.) was administered to the treatment group 1 h before clamping the hepatic hilum, at clamping, at reperfusion, and at 1 and 2 h after reperfusion. The control animals received normal saline and an i.v. infusion. Liver function tests and analysis of serum, erythrocyte, and tissue malondialdehyde contents were performed at commencement of laparotomy, before reperfusion, and at 30 min and 7 days after reperfusion. Liver biopsies were taken at laparotomy, at 30 min, and at 7 days after reperfusion for histological and ultrastructural examination. Assessment of apoptosis included in situ end-labelling analysis and DNA gel electrophoresis. Survival at 7 days was better in the treated animals than in the controls (9/10 vs. 7/12). Tissue malondialdehyde content, aspartate aminotransferase, and lactate dehydrogenase levels were lower in the treatment group, in which morphological changes were significantly less evident than in the controls 30 min after reperfusion. At 7 days, differences between the groups with respect to cell integrity were apparent only on ultrastructural analysis. Glycogen content, 7 days after reperfusion, was higher in the treatment group than in the controls: 70.25 per cent vs. 21.66 per cent positive hepatocytes (score 3 vs. score 1). Multiparametric analysis showed fewer apoptotic cells in the treatment group at all times. Our data show that the administration of L-arginine reduces damage to liver tissue after ischaemia/reperfusion injury in a pig model. This may be explained not only by the known vasodilator, anti-aggregation, and superoxide inactivation effects of increased nitric oxide release, but possibly also by some other action of L-arginine, such as its influence on cellular metabolism.
Calabrese
F
F
Department of Pathology, University Hospital of Padua, Medical School, Italy.
Valente
M
M
Pettenazzo
E
E
Ferraresso
M
M
Burra
P
P
Cadrobbi
R
R
Cardin
R
R
Bacelle
L
L
Parnigotto
A
A
Rigotti
P
P
D000818:Animals; D017209:Apoptosis; D001120:Arginine / Q000627:therapeutic use*; D005260:Female; D017403:In Situ Hybridization; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000648:ultrastructure; D008315:Malondialdehyde / Q000097:blood; D008854:Microscopy, Electron; D009336:Necrosis; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D015996:Survival Rate; D013552:Swine
D008315:Malondialdehyde; D001120:Arginine