Alternations in liver hemodynamics in an intact porcine model of endotoxin shock

Abstract

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 (Pback) in each bed in an intact porcine model of endotoxemia. Slope and Pback 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 Pback. The HA buffer response (HABR), defined as a decrease in HA resistance produced by reduction in PV flow (Qpv), was abolished at t = 90 min. The PV Pback 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 Pback 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 Qpv 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 Qpv.(ABSTRACT TRUNCATED AT 250 WORDS)

The Influence of Phosphodiesterase Inhibitor, Rolipram, on Hemodynamics in Lipopolysaccharide-Treated Rats

“…In addition, there were no significant changes in heart rate. Thus, it is possible that the reduction in cardiac output observed in animals treated with LPS in the present investigation was the result of a reduction in venous return (2,21). Moreover, it is possible that treatment with rolipram and dexamethasone augmented venous return, thereby resulting in the maintenance of cardiac output in LPS-treated rats.…”

“…Reportedly, treatment of rats with LPS did not appear to significantly affect arterial resistance or resistance to venous return (2). However, endotoxic shock has been reported to lead to an impairment of portal venous flow with increased portal venous resistance causing an increase in splanchnic blood pooling and subsequent decrease in venous return and thus cardiac output in anesthetized pigs (21). Taken together, the evidence would suggest that the reduction in cardiac output in endotoxic shock is, in part, due to a reduction in venomotor tone.…”

Effects of cardiac preload reduction and dobutamine on hepatosplanchnic blood flow regulation in porcine endotoxemia

“…In our study, we found a decreased but still detectable HABR after 18 h of endotoxin infusion, which did not further deteriorate during continued endotoxin infusion. It has been shown that hepatic arterial resistance is increased for a given portal venous flow after several hours of endotoxin infusion (1). Lipopolysaccharide infusion decreases mRNA levels of constitutive nitric oxide synthase in liver tissue (37), and administration of the nitric oxide donor sodium nitroprusside during endotoxemia is able to both improve hepatic arterial flow and restore the autoregulatory response of the hepatic artery following reduction of hepatic blood flow (15,37).…”

The NO Donor Sodium Nitroprusside Reverses the Negative Effects on Hepatic Arterial Flow Induced by Endotoxin and the NO Synthase Inhibitor L-NAME

“…Accumulating evidence suggests that endo toxin induces a dysfunction of the hepatic arterial buffer response [29,30]. So far the mechanisms have been partly unresolved.…”

“…endotox emia) have the potential to abolish or reduce this effect and instead direct vasoconstriction at the underlying smooth muscle [32,33], This may explain that hepatic arterial resis tance tended to increase during edotoxin infu sion, although the values did not reach statis tical significance. Other investigators report conflicting results on this point, probably re lated to the duration of endotoxemia [14,30,34], The subsequent injection of the nonselective NOS inhibitor L-NAME nearly dou bled hepatic arterial resistance, indicating that the endogenous local production of NO was maintained at a sufficient level to have considerable effects upon hepatic circulation. It may be anticipated that suppression of endothelial NO production in this and similar situations will aggravate liver injury by reduc ing and perturbing microcirculation.…”