Effects of selective iNOS inhibition on gut and liver O2-exchange and energy metabolism during hyperdynamic porcine endotoxemia.

Abstract

We have previously demonstrated that non-selective nitric oxide synthase (NOS) inhibition did not reverse the LPS-induced deterioration of hepato-splanchnic energy status in porcine endotoxic shock. Therefore, this study investigated the effect of selective inducible NOS (iNOS) inhibition using 1400 W on intestinal and liver perfusion, O2 kinetics, and energy metabolism during hyperdynamic porcine endotoxemia. Intravenous E. Coli LPS was continuously infused over 24 h concomitant with fluid resuscitation. After 12 h of endotoxemia, continuous intravenous infusion of 1400 W was started until the end of the experiment and was titrated to maintain mean blood pressure (MAP) at baseline levels. Twelve, 18, and 24 h after starting LPS, we measured hepatic arterial and portal venous blood flow, ileal mucosal-arterial PCO2 gap, portal as well as hepatic venous lactate/pyruvate ratios, and endogenous glucose production rate. Expired NO and plasma nitrate levels were assessed as a measure of NO production. 1400 W decreased LPS-induced increase in expired NO and allowed for the maintenance of MAP without modification of cardiac output. Despite unchanged regional macrocirculation, 1400 W prevented the progressive rise of ileal mucosal-arterial PCO2 gap, significantly improved the LPS-induced impairment of hepato-splanchnic redox state, and blunted the decline in liver lactate clearance. Increased glucose production rate was not influenced. Thus, the selective iNOS inhibition with 1400 W prevented circulatory failure and largely attenuated otherwise progressive LPS-induced deterioration of intestinal and hepatocellular energy metabolism.

• Authors: M Matejovic, P Radermacher, I Tugtekin, A Stehr, M Theisen, J Vogt, U Wachter, F Ploner, M Georgieff, K Träger
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 16 Issue 3 Pg. 203-10 (Sep 2001) ISSN: 1073-2322 [Print] United States
• PMID: 11531022 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amidines
• Benzylamines
• Enzyme Inhibitors
• N-(3-(aminomethyl)benzyl)acetamidine
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Oxygen

Topics

• Amidines (pharmacology)
• Animals
• Benzylamines (pharmacology)
• Digestive System (drug effects, metabolism)
• Endotoxemia (drug therapy, metabolism, physiopathology)
• Energy Metabolism (drug effects)
• Enzyme Inhibitors (pharmacology)
• Female
• Hemodynamics
• Intestinal Mucosa (metabolism)
• Intestines (drug effects)
• Liver (drug effects, metabolism)
• Male
• Nitric Oxide Synthase (antagonists & inhibitors, metabolism)
• Nitric Oxide Synthase Type II
• Oxygen (metabolism)
• Perfusion
• Swine