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.