Inducible nitric oxide synthase inhibition improves intestinal microcirculatory oxygenation and CO₂ balance during endotoxemia in pigs

Objective: We examined whether selective inhibition of inducible nitric oxide synthase (iNOS) promotes intestinal microvascular oxygenation (μPO ₂) and CO₂ off-load after endotoxic shock. Design and setting: Prospective, controlled experimental study in a university animal research laboratory. Subjects: 13 domestic pigs. Interventions: After baseline measurements shock was induced by 1 μg kg^-1 h^-1 endotoxin until mean arterial pressure fell below 60 mmHg. After 30 min in shock the animals were resuscitated with either fluid alone (control, n=6) or fluid and the iNOS inhibitor N-[3-(aminomethyl)benzyl]acetamidine hydrochloride (1400W, n=7). As final experimental intervention all animals received the nonselective NOS inhibitor L-NAME. Measurements and results: Systemic and regional hemodynamic and oxygenation parameters were measured at baseline, during endotoxemia and shock, hourly for 3 h of 1400W therapy, and 30 min after the final L-NAME administration. μPO₂ was assessed by the Pd-porphyrin phosphorescence technique, and the arterial to intestinal PCO ₂ gap was determined by air tonometry. Endotoxemia and shock resulted in a decrease in ileal mucosal and serosal μPO₂ and a rise in PCO₂ gap. The combination of 1400W and fluid resuscitation, but not fluid alone, normalized both the serosal μPO₂ and the intestinal PCO₂ gap. Administration of L-NAME decreased cardiac output and oxygen delivery and intestinal μPO₂ and blood flow in both groups. Conclusions: Partial blockade of NO production by 1400W increased serosal microvascular oxygenation and decreased the intestinal CO₂ gap. This findings are consistent with the idea that 1400W corrects pathological flow distribution and regional dysoxia within the intestinal wall following endotoxic shock.