BACKGROUND: Inhibition of nitric oxide synthase (NOS) has been claimed to be beneficial in septic shock. We investigated the overall and regional effects 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 superior mesenteric artery. Thirteen animals were given a 3-h infusion of endotoxin; in 6 of these an infusion of NG-nitro-L-arginine-methyl-ester (L-NAME) was started an hour after the start of endotoxin while 7 animals served as controls and received endotoxin only. Six animals were sham operated with 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 vascular resistance. The infusion of endotoxin caused a decrease in flows in all regions. 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 ratio, 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. Lactate levels increased with no differences between the groups. CONCLUSION: In hypodynamic endotoxic shock, L-NAME infusion enhanced pulmonary vasoconstriction and increased left ventricular afterload. The resulting hypoperfusion caused an increase in mortality. The effects of L-NAME on global and mesenteric blood flow and metabolism were similar, while L-NAME had no additional effects on hepatic hypoperfusion or oxygen extraction. Thus, nitric oxide does not seem to be a major factor in the preservation of hepatic perfusion during unresuscitated endotoxic shock.
BACKGROUND: Inhibition of nitric oxide synthase (NOS) has been claimed to be beneficial in septic shock. We investigated the overall and regional effects 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 superior mesenteric artery. Thirteen animals were given a 3-h infusion of endotoxin; in 6 of these an infusion of NG-nitro-L-arginine-methyl-ester (L-NAME) was started an hour after the start of endotoxin while 7 animals served as controls and received endotoxin only. Six animals were sham operated with 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 vascular resistance. The infusion of endotoxin caused a decrease in flows in all regions. 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 ratio, 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. Lactate levels increased with no differences between the groups. CONCLUSION: In hypodynamic endotoxic shock, L-NAME infusion enhanced pulmonary vasoconstriction and increased left ventricular afterload. The resulting hypoperfusion caused an increase in mortality. The effects of L-NAME on global and mesenteric blood flow and metabolism were similar, while L-NAME had no additional effects on hepatic hypoperfusion or oxygen extraction. Thus, nitric oxide does not seem to be a major factor in the preservation of hepatic perfusion during unresuscitated endotoxic shock.
Authors: Joshua J Corrigan; Monique T Fonseca; Elizabeth A Flatow; Kevin Lewis; Alexandre A Steiner Journal: J Physiol Date: 2014-06-20 Impact factor: 5.182
Authors: Yan Li; Xuemei Li; Michael Haley; Yvonne Fitz; Eric Gerstenberger; Steven M Banks; Peter Q Eichacker; Xizhong Cui Journal: Intensive Care Med Date: 2006-06-15 Impact factor: 17.440
Authors: A Stehr; F Ploner; I Tugtekin; M Matejovic; M Theisen; C Zülke; M Georgieff; P Radermacher; K-W Jauch Journal: Intensive Care Med Date: 2003-05-09 Impact factor: 17.440