Preventive effect of preoperative portal vein ligation on endotoxin-induced hepatic failure in hepatectomized rats is associated with reduced tumour necrosis factor alpha production.

Abstract

Preoperative portal vein embolization successfully reduces the incidence of postoperative hepatic failure in which endotoxin is postulated to be involved. To identify the mechanism of this preventive effect, the relationship of endotoxin-induced liver injury with tumour necrosis factor (TNF) alpha and nitric oxide production in the peripheral blood, liver and spleen of rats subjected to preoperative portal vein branch ligation (PVL) was compared with that in rats undergoing sham operation. Rats with PVL and those that underwent sham operation were subjected to resection of ligated liver lobes (PVL-Hx rats) and two-thirds hepatectomy (noPVL-Hx rats) respectively at day 5, followed by intravenous administration of endotoxin 200 microgram/kg body-weight at day 7. At various time intervals after endotoxin injection, the peripheral blood, liver and spleen tissues were harvested and analysed for TNF-alpha and nitric oxide production. The survival rates of noPVL-Hx and PVL-Hx rats at 48 h after endotoxin administration were 40 and 100 per cent respectively. The former rats showed more extensive liver injury as represented by higher serum aminotransferase and hyaluronate levels than the latter. Plasma concentrations of TNF-alpha at 1.5 h after endotoxin treatment were significantly higher in noPVL-Hx rats (mean(s.e.m.) 22 125(2175) pg/ml; n = 6) than PVL-Hx rats (8344(4076) pg/ml; n = 6) (P < 0.01). Consistent with this, expression of TNF-alpha messenger RNA in the liver and spleen was suppressed in PVL-Hx rats. In two-thirds hepatectomized rats, plasma TNF-alpha concentrations after endotoxin administration at 1, 2 and 3 days (14 350(2186), 26 375(2478) and 23 000(3745) pg/ml respectively; n = 6 each) were significantly higher than that before operation (9067(1559) pg/ml; n = 6) (P < 0.05), whereas those at 5 and 7 days (10 102(3616) and 8580(1427) pg/ml respectively; n = 6 each) showed no significant increase. Furthermore, nitric oxide production in peripheral blood and liver was suppressed by preoperative PVL. Prevention of endotoxin-induced liver failure by preoperative PVL is associated with reduced production of TNF-alpha in the later phase of liver regeneration.