ALTERATIONS IN LIVER HEMODYNAMICS IN AN INTACT PORCINE MODEL OF ENDOTOXIN-SHOCK

Septic shock decreases preload, increases splanchnic blood pooling and edema formation, and induces hepatic dysfunction. We hypothesized that the hemodynamic effects of endotoxemic shock on the portal venous (PV) and hepatic arterial (HA) vascular beds contribute to this picture. Multipoint pressure-flow relationships were generated to evaluate the slope (resistance or conductance) and effective back pressure (P-back) in each bed in an intact porcine model of endotoxemia. Slope and P-back were determined during endotoxemia over 300 min (n = 8) and compared with sham-treated control studies (n = 5). At time (t) = 60 min, HA slope significantly decreased (P < 0.05) without a change in P-back. The HA buffer response (HABR), defined as a decrease in HA resistance produced by reduction in PV flow (Q(pv)), was abolished at t = 90 min. The PV P-back significantly increased without a change in PV slope. At t = 300 min, HA slope returned to baseline, and the HABR was present while PV slope and P-back increased (P < 0.05). Fractional flow (flow relative to cardiac output) was constant except for a transient increase in HA fractional flow at t = 60 min. Histological studies showed focal necrosis and hemorrhage without evidence of vasoconstriction or thrombosis. In conclusion, endotoxic shock leads to time-dependent impairment of Q(pv) with increased PV resistance, causing an increase in splanchnic blood pooling and subsequent decrease in venous return. The HA bed is dilated early with an absent HABR. Later an HABR is present but defined by increased HA resistance for a given Q(pv). These alterations in hemodynamic homeostasis help to account for the specific involvement of the splanchnic bed in septic shock, the high incidence of liver dysfunction, and, if generalized to other organ beds, the roles of arterial and venous compartments in sepsis.