Protective role of nitric oxide in ischemia and reperfusion injury of the liver

Background: The suppressed production of nitric oxide (NO), associated with endothelial dysfunction, is thought to be a cause of ischemia and reperfus ion injury of the liver. But findings of the salutary effects of NO enhance ment on such injury have been conflicting. In this study, we tested our hyp othesis that NO enhancement would attenuate ischemic liver injury. For this ,purpose, an NO precursor, L-arginine, and a novel NO donor, FK409, were ap plied to a 2-hour total hepatic vascular exclusion model in dogs. Study Design: L-arginine was administered TV at a dose of 100 mg/kg twice ( n = 5), while 300 mg/kg twice of FK409 was infused continuously into the po rtal vein (n = 5). The drugs were given to the animals for 30 and 60 minute s before and after ischemia, respectively. Nontreated animals were used as the control (n = 10). Two-week survival, systemic and hepatic hemodynamics indices, liver function tests, energy metabolism, and histopathology were a nalyzed. Results: Both treatments comparably augmented hepatic tissue blood flow dec reased liver enzyme release, and increased high-energy phosphate restoratio n during the reperfusion period, all of which contributed to rescuing all o f the treated animals from the 2-hour total hepatic ischemia. In contrast, ischemia caused 70% mortality in the control group. Histologically, structu ral abnormality and neutrophil infiltration were markedly attenuated by the treatments. Systemic hypotension was observed in the animals treated with FK409, however. Conclusions: Our data demonstrate that NO enhancement alleviates the liver injury caused by ischemia and reperfusion. The supplementation of L-arginin e, rather than FK409, is considered more applicable to clinical use because of the absence of systemic adverse effects. (J Am Coll Surg 1999;188:43-52 . (C) 1999 by the American College of Surgeons).