Dysregulation of the veno-arterial response in the superior mesenteric artery during endotoxic shock.

OBJECTIVE

To investigate whether the vascular dysfunction in endotoxic shock is associated with inhibition of the veno-arterial response of the superior mesenteric artery.

DESIGN

Prospective, concurrent trial.

SETTING

Animal laboratory.

SUBJECTS

Domestic pigs.

INTERVENTIONS

Two groups of pigs were anesthetized with ketamine and pentobarbital, mechanically ventilated, and hemodynamically monitored. One group (n = 8) was challenged with Escherichia coli endotoxin (30 micrograms/kg iv), while the other group (n = 4) served as time controls. Portal vein pressure was transiently increased in a series of steps from baseline to 25 mm Hg by partially obstructing portal venous flow.

MEASUREMENTS AND MAIN RESULTS

The effects of increases in portal pressure on superior mesenteric artery resistance, superior mesenteric artery fractional flow, and cardiac output were assessed. Under pre-endotoxin conditions, raising portal pressure induced an increase in superior mesenteric artery resistance, a decrease in superior mesenteric artery fractional flow, and no significant change in cardiac output (i.e., a normally regulating veno-arterial response). After endotoxin administration, raising portal pressure induced a decrease in superior mesenteric artery resistance, no change in superior mesenteric artery fractional flow, and a decrease in cardiac output (i.e., a dysregulated veno-arterial response).

CONCLUSIONS

Under baseline conditions, a normally regulating veno-arterial response in the mesenteric vascular bed should minimize intestinal blood pooling with acute portal hypertension. Under conditions of endotoxemic shock, the dysregulation of the veno-arterial response could substantially contribute to blood pooling and edema formation in the intestinal vascular bed during septic shock. This phenomenon may account for many of the macro- and microcirculatory manifestations of septic shock.