Effects of selective iNOS inhibition on gut and liver O-2-exchange and energy metabolism during hyperdynamic porcine endotoxemia

Citation
M. Matejovic et al., Effects of selective iNOS inhibition on gut and liver O-2-exchange and energy metabolism during hyperdynamic porcine endotoxemia, SHOCK, 16(3), 2001, pp. 203-210
Citations number
43
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Aneshtesia & Intensive Care","Cardiovascular & Hematology Research
Journal title
SHOCK
ISSN journal
1073-2322 → ACNP
Volume
16
Issue
3
Year of publication
2001
Pages
203 - 210
Database
ISI
SICI code
1073-2322(200109)16:3<203:EOSIIO>2.0.ZU;2-K
Abstract
We have previously demonstrated that non-selective nitric oxide synthase (N OS) inhibition did not reverse the LPS-induced deterioration of hepato-spla nchnic energy status in porcine endotoxic shock. Therefore, this study inve stigated the effect of selective inducible NOS (iNOS) inhibition using 1400 W on intestinal and liver perfusion, O-2 kinetics, and energy metabolism du ring hyperdynamic porcine endotoxemia. Intravenous E. Coli LPS was continuo usly infused over 24 h concomitant with fluid resuscitation. After 12 h of endotoxemia, continuous intravenous infusion of 1400W was started until the end of the experiment and was titrated to maintain mean blood pressure (MA P) 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 endogen ous glucose production rate. Expired NO and plasma nitrate levels were asse ssed as a measure of NO production. 1400W decreased LPS-induced increase in expired NO and allowed for the maintenance of MAP without modification of cardiac output. Despite unchanged regional macrocirculation, 1400W prevente d the progressive rise of ileal mucosal-arterial PCO2 gap, significantly im proved the LPS-induced impairment of hepato-splanchnic redox state, and blu nted the decline in liver lactate clearance. Increased glucose production r ate was not influenced. Thus, the selective NOS inhibition with 1400W preve nted circulatory failure and largely attenuated otherwise progressive LPS-i nduced deterioration of intestinal and hepatocellular energy metabolism.