Intestinal and hepatic perfusion and metabolism in hypodynamic endotoxic shock. Effects of nitric oxide synthase inhibition

Background: Inhibition of nitric oxide synthase (NOS) has been claimed to b e beneficial in septic shock. We investigated the overall and regional effe cts of a NOS-inhibitor on perfusion and metabolism during severe endotoxic shock. Methods: Nineteen anaesthetised pigs were catheterised and ultrasonic flow- probes were placed around the portal vein, the hepatic artery, and the supe rior mesenteric artery. Thirteen animals were given a 3-h infusion of endot oxin; in 6 of these an infusion of N-G-nitro-L-arginine-methyl-ester (L-NAM E) was started an hour after the start of endotoxin while 7 animals served as controls and received endotoxin only. Six animals were sham operated wit h no further intervention. Results: Endotoxin produced a hypodynamic shock with pulmonary hypertension . L-NAME did not increase arterial blood pressure, but deepened the fall in cardiac output and enhanced the increase in systemic and pulmonary vascula r resistance. The infusion of endotoxin caused a decrease in flows in all r egions. The addition of L-NAME induced a further decrease in the mesenteric artery flow only. L-NAME had no additional effect on hepatic artery flow r atio, while a transient decrease was seen in mesenteric flow ratio. Portal flow ratio decreased in the control group only. Global as well as regional oxygen extraction increased in both groups, more so in the L-NAME group. La ctate levels increased with no differences between the groups. Conclusion: In hypodynamic endotoxic shock, L-NAME infusion enhanced pulmon ary vasoconstriction and increased left ventricular afterload. The resultin g hypoperfusion caused an increase in mortality. The effects of L-NAME on g lobal and mesenteric blood flow and metabolism were similar, while L-NAME h ad no additional effects on hepatic hypoperfusion or oxygen extraction. Thu s, nitric oxide does not seem to be a major factor in the preservation of h epatic perfusion during unresuscitated endotoxic shock.