Effect of increased cardiac output on liver blood flow, oxygen exchange and metabolic rate during longterm endotoxin‐induced shock in pigs

We investigated hepatic blood flow, O 2 exchange and metabolism in porcine endotoxic shock (Control, n =8; Endotoxin, n =10) with administration of hydroxyethylstarch to maintain arterial pressure (MAP)>60 mmHg. Before and 12, 18 and 24 h after starting continuous i.v. endotoxin we measured portal venous and hepatic arterial blood flow, intracapillary haemoglobin O 2 saturation (Hb‐O 2 %) of the liver surface and arterial, portal and hepatic venous lactate, pyruvate, glyercol and alanine concentrations. Glucose production rate was derived from the plasma isotope enrichment during infusion of [6,6‐ 2 H 2 ]‐glucose. Despite a sustained 50% increase in cardiac output endotoxin caused a progressive, significant fall in MAP. Liver blood flow significantly increased, but endotoxin affected neither hepatic O 2 delivery and uptake nor mean intracapillary Hb‐O 2 % and Hb‐O 2 % frequency distributions. Endotoxin nearly doubled endogenous glucose production rate while hepatic lactate, alanine and glycerol uptake rates progressively decreased significantly. The lactate uptake rate even became negative ( P <0.05 vs Control). Endotoxin caused portal and hepatic venous pH to fall significantly concomitant with significantly increased arterial, portal and hepatic venous lactate/pyruvate ratios. During endotoxic shock increased cardiac output achieved by colloid infusion maintained elevated liver blood flow and thereby macro‐ and microcirculatory O 2 supply. Glucose production rate nearly doubled with complete dissociation of hepatic uptake of glucogenic precursors and glucose release. Despite well‐preserved capillary oxygenation increased lactate/pyruvate ratios reflecting impaired cytosolic redox state suggested deranged liver energy balance, possibly due to the O 2 requirements of gluconeogenesis.British Journal of Pharmacology (1998) 124 , 1689–1697; doi: 10.1038/sj.bjp.0701998