Mechanisms of inducible nitric oxide synthase (iNOS) inhibition-related improvement of gut mucosal acidosis during hyperdynamic porcine endotoxemia

Objective: To determine the mechanisms of improved gut mucosal acidosis associated with selective inducible nitric oxide synthase (iNOS) inhibition. Design: Prospective, controlled experimental study. Setting: Animal research laboratory. Animals: Fourteen domestic pigs. Interventions: Anesthetized and mechanically ventilated pigs received continuous i.v. endotoxin for 24 h. A selective iNOS-inhibitor (140OW, n=8) or vehicle (control, n=6) was started at 12 h of endotoxin and infused until the end of the experiment. Measurements and results: Before as well as at 12 and 24 h of endotoxin, portal venous flow (ultrasound probe), intestinal oxygen (02) extraction, portal venous-arterial carbon dioxide (CO2) content difference and ileal mucosal-arterial PCO2 gap (fiberoptic sensor) were assessed together with video recordings of the villous microcirculation (number of perfused/unperfused villi) using orthogonal polarization spectral imaging via an ileostomy. The gut wall microvascular blood flow (units) and hemoglobin O-2 saturation (muHb-O-2) were assessed with a combined laser Doppler flow and remission spectrophotometry probe. 140OW blunted the otherwise progressive rise in the PCO2 gap without affecting portal venous flow, regional O-2 and CO2 exchange or the number of unperfused villi. While endotoxin markedly aggravated the heterogeneity of the microvascular blood flow and oxygenation, 140OW had no further effect. Conclusions: Given the uninfluenced parameters of the ileal mucosal microcirculation in our model of long-term porcine endotoxemia, selective iNOS inhibition probably improved the PCO2 gap due to a redistribution of the microvascular perfusion within the gut wall and/or an amelioration of the cellular respiration.