Warm hepatic ischemia in pigs: effects of L-arginine and oligotide treatment.
Reperfusion injury represents a key event leading to graft nonfunction. Maintaining adequate nitric oxide levels and stimulating vasodilator synthesis can probably minimize endothelial damage. The aim of this study was to investigate the effect of L-arginine, a substrate of nitric oxide synthesis, and oligotide, a promoter of prostacyclin synthesis, on liver function and morphology after warm ischemia-reperfusion injury. After constructing a side-to-side portacaval shunt, ischemia was induced by clamping the hepatic hilum for 2 h above the shunt, in 19 female pigs divided into a control group (n = 7), an L-arginine treatment group (n = 6), and an oligotide treatment group (n = 6). Liver function tests and measurements of serum and red blood cell malondialdehyde and plasma nitric oxide levels were performed before reperfusion and at 1, 10, 60, and 120 min after reperfusion. Liver biopsies, taken before reperfusion and at 30 min and 7 days after reperfusion, were analyzed for tissue malondialdehyde, histological-ultrastructural features, and apoptosis evaluation. Thirty minutes after reperfusion, liver malondialdehyde, sinusoidal congestion, necrosis, and apoptosis were significantly lower in the L-arginine group than in the controls (p < .05). On postoperative day 7, tissue malondialdehyde decreased, while plasma nitric oxide and hepatocyte glycogen content were increased in the L-arginine group compared to controls (p < .05). This study demonstrates the protective effect of L-arginine on hepatic lipoperoxidation and liver morphology in a pig model of warm ischemia-reperfusion injury. The increased plasma levels of nitric oxide a week after ischemia-reperfusion injury support the hypothesis that it has a role in preventing liver damage. The same beneficial effect was not confirmed for oligotide.
Burra
P
P
Dipartimento di Scienze Chirurgiche e Gastroenterologiche, Università degli Studi di Padova, Italy. burra@unipd.it
Chirizzi
L
L
Cardin
R
R
Cadrobbi
R
R
Baldan
N
N
Calabrese
F
F
Pettenazzo
E
E
Calò
L
L
Plebani
M
M
Rigotti
P
P
D000818:Animals; D017209:Apoptosis; D001120:Arginine / Q000494:pharmacology*; D005260:Female; D007511:Ischemia / Q000378:metabolism / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000648:ultrastructure; D009569:Nitric Oxide / Q000032:analysis / Q000502:physiology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine
D009838:Oligodeoxyribonucleotides; D020011:Protective Agents; C099595:oligotide; D009569:Nitric Oxide; D001120:Arginine