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

The peripheral vascular response to sepsis is characterized by a vasodilatation of the systemic arterial vessels. Pulmonary hypertension with an increase in resistance and back pressure to flow defined by pressure-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 anesthetized pigs (n = 8), the liver was vascularly isolated and perfused. Steady-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 of the P-Q relationships were obtained by least squares linear regression analysis. Endotoxemia increased PV Pback (P < 0.05), and Pback always exceeded Pout (P < 0.05) when the latter was raised. In contrast, in controls, no difference was observed between Pback and Pout when the latter was raised. Endotoxemia also increased the PV slope compared with 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 the HA, endotoxin caused a decrease in slope but did not alter Pback. The simultaneous increase in the PV Pback and slope that occurs with endotoxemia decreases splanchnic venous return, pooling blood in the splanchnic compartment for a given total blood volume. Raising Pout (e.g., volume resuscitation) decreases PV slope and is expected to restore venous return but does not overcome the positive gradient between PV Pback and Pout present with endotoxemia. These results suggest that the liver plays an important role in the macrocirculatory manifestations of sepsis, including low cardiac output and sequestration of blood in the splanchnic compartment.