Effect of combining nicotinamide as a PARS-inhibitor with selective iNOS blockade during porcine endotoxemia

摘要: To investigate the effects of combined selective inducible nitric oxide synthase (iNOS) inhibition using 1400 W with nicotinamide (NAD) as a PARS-inhibitor on hepato-splanchnic hemodynamics, O2 kinetics, and energy metabolism during hyperdynamic porcine endotoxemia. Prospective, randomized, controlled, interventional experiment. Animal research laboratory. Seventeen domestic pigs. After 12 h continuous i.v. endotoxin (LPS) infusion 17 pigs received either no drug (CON, n=9) or 1400 W, titrated to maintain mean arterial pressure (MAP) at pre-endotoxin level, plus 10 mg·kg·h NAD (n=8;). Measurements were obtained before, 12 h, 18 h, 24 h after starting LPS infusion. In addition systemic pulmonary hemodynamics gas exchange, we measured hepatic portal venous blood flow, liver drained viscera ileal mucosal-arterial PCO2 gap, well lactate/pyruvate ratios. Expired NO plasma nitrate levels assessed parameter production. Without affecting cardiac output, therapy maintained MAP blunted LPS-induced rise in expired levels, attenuated progressive fall lactate clearance, impairment redox state. The gap was not influenced. Combining iNOS PARS blocker may prevent circulatory failure attenuate detrimental consequences intestinal hepatocellular metabolism. Given potential hepatotoxicity high-dose treatment, more potent blockers higher selectivity might further enhance benefit this therapeutic approach.