EFFECTS OF ENDOTOXIN ON ISOLATED PORCINE LIVER - PRESSURE-FLOW ANALYSIS

The peripheral vascular response to sepsis is characterized by a vasod ilatation of the systemic arterial vessels. Pulmonary hypertension wit h an increase in resistance and back pressure to flow defined by press ure-flow (P-Q) relationships has been reported in experimental sepsis. We hypothesized that endotoxin can induce differential alterations in resistance and back pressure to flow in the liver venous and arterial beds. Ninety minutes after endotoxin administration in intact anesthe tized pigs (n = 8), the liver was vascularly isolated and perfused. St eady-state P-Q relationships in both the portal vein (PV) and hepatic artery (HA) were generated at multiple outflow pressures (Pout; 0, 5, 10, and 15 mmHg) and compared with those obtained in control livers (n = 6). Extrapolated zero-flow pressure intercepts (Pback) and slopes o f the P-Q relationships were obtained by least squares linear regressi on analysis. Endotoxemia increased PV Pback (P < 0.05), and Pback alwa ys exceeded Pout (P < 0.05) when the latter was raised. In contrast, i n controls, no difference was observed between Pback and Pout when the latter was raised. Endotoxemia also increased the PV slope compared w ith control. Raising Pout from 0 to 15 mmHg decreased PV slope in the endotoxin group to a greater degree than in controls (P < 0.05). In th e HA, endotoxin caused a decrease in slope but did not alter Pback. Th e simultaneous increase in the PV Pback and slope that occurs with end otoxemia decreases splanchnic venous return, pooling blood in the spla nchnic compartment for a given total blood volume. Raising Pout (e.g., volume resuscitation) decreases PV slope and is expected to restore v enous return but does not overcome the positive gradient between PV Pb ack and Pout present with endotoxemia. These results suggest that the liver plays an important role in the macrocirculatory manifestations o f sepsis, including low cardiac output and sequestration of blood in t he splanchnic compartment.