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).