Inducible nitric oxide synthase inhibition improves intestinal microcirculatory oxygenation and CO2 balance during endotoxemia in pigs
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We examined whether selective inhibition of inducible nitric oxide synthase (iNOS) promotes intestinal microvascular oxygenation (µPO2) and CO2 off-load after endotoxic shock.
Design and setting
Prospective, controlled experimental study in a university animal research laboratory.
13 domestic pigs.
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 PCO2 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.
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.
KeywordsShock, septic Endotoxemia, physiopathology Regional blood flow, drug effects Microcirculation, physiopathology Oxygen consumption, drug effects Nitric-oxide synthase
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