Opposite effects of prostacyclin on hepatic blood flow and oxygen consumption after burn and sepsis

Burn and sepsis are associated with hepatic ischemia and reperfusion injury. This study examines the hypothesis that postburn treatment with the vasodilator prostacyclin would be beneficial for hepatic perfusion and oxygenation.

Female pigs (n = 18, 20-25 kg) underwent laparotomy, during which ultrasonic flow probes were placed on the portal vein and the common hepatic artery. Catheters were inserted in the superior mesenteric and left hepatic veins. After 5 days, all animals were anesthetized and 12 of them received 40% total body surface area third-degree burn; 100 microg/kg Escherichia coli lipopolysaccharide (LPS) was intravenously administered 18 hours postburn. Burned animals were randomized to receive a constant infusion of iloprost (20 ng/kg per minute) or an equivalent amount of carrier solution (normal saline). All animals were studied for 42 hours.

Burn caused a 2.5-fold increase in hepatic arterial vascular resistance (HAVR) and a 39% decrease in hepatic arterial blood flow (HABF). Postburn administration of iloprost did not improve the hepatic arterial hemodynamics (1.8-fold increase in HAVR and 38% decrease in HABF). Post-LPS, HABF was significantly reduced to 22% of baseline and HAVR was 15-fold increased (P < 0.05 vs. baseline, ANOVA). In contrast, iloprost-treated animals did not show hepatic arterial vasoconstriction, as both HABF and HAVR remained baseline values during the endotoxic phase (P < 0.05 vs. nontreated group, ANOVA). Postburn iloprost treatment yielded a significant improvement in post-LPS portal venous blood flow (PVBF, 79% of baseline vs. 45% of baseline in nontreated animals, P < 0.05, ANOVA). Portal venous pressure showed 16% and 56% increases after burn and endotoxin, respectively. Portal hypertension did not occur in iloprost-treated animals, as portal venous pressure remained within baseline range (P < 0.05 vs. nontreated group, ANOVA). Burn and endotoxemia resulted in a significant decrease of hepatic oxygen delivery (hDO2, 63% and 12% of baseline, respectively) and hepatic oxygen consumption (hVO2, 61% and 21% of baseline, respectively). Only during the postburn endotoxic phase, iloprost improved hDO2 and hVO2 (140% and 79%, respectively; P < 0.05 vs. nontreated group, ANOVA).

Postburn prostacyclin treatment appears to have no beneficial effects on hepatic perfusion early postburn. However, during the late postburn endotoxic phase, prostacyclin seems to significantly improve hepatic total blood flow and oxygenation. In addition, prostacyclin treatment attenuated burn- and endotoxin-induced portal hypertension.