Norepinephrine and N-G-monomethyl-L-arginine in hyperdynamic septic shock in pigs: Effects on intestinal oxygen exchange and energy balance

Objectives: To compare the effects of norepinephrine (NOR) and the nonselec tive nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), on intestinal blood flow, oxygen exchange, and energy metabolism over 24 hrs of hyperdynamic, normotensive porcine endotoxic shock. Design: Prospective, randomized, experimental study with repeated measures. Setting: Investigational animal laboratory. Subjects: Twenty-seven pigs were divided into three groups: seven animals r eceived no vasopressor therapy (ETX) during endotoxic shock; ten animals we re treated with NOR; and ten animals were treated with L-NMMA. Interventions: Pigs were anesthetized, mechanically ventilated, and instrum ented. Eight hours later, endotoxic shock was initiated by an infusion of E scherichia coli lipopolysaccharide. Animals were resuscitated by hetastarch directed to maintain the intrathoracic blood volume and a mean arterial pr essure (MAP) of >60 mm Hg. Twelve hours after the start of the endotoxin in fusion, NOR or L-NMMA was administered for 12 hrs in the treatment groups t o maintain a MAP at preshock levels, Measurements and Main Results:ETX caused a continuous fall in MAP, despite a sustained increase in the cardiac output achieved by fluid resuscitation. NOR maintained MAP at preshock levels because of a further rise in cardiac output, whereas hemodynamic stabilization during L-NMMA resulted from syst emic vasoconstriction. NOR increased portal Venous blood flow concomitant w ith decreased intestinal oxygen extraction, whereas L-NMMA influenced neith er portal venous blood flow nor intestinal oxygen extraction. Mean capillar y hemoglobin oxygen saturation of the ileal mucosa as well as the frequency distributions reflecting microcirculatory oxygen availability remained unc hanged as well. Nevertheless, portal venous pH similarly decreased and port al venous lactate/pyruvate ratios increased in all three groups. The arteri al-ileal mucosal Pco(2) gap progressively increased in the ETX and L-NMMA g roups, whereas NOR blunted this response. Conclusions: Neither treatment could reverse the ETX-induced derangements o f cellular energy metabolism as reflected by the increased portal venous la ctate/pyruvate ratios. The NOR-induced attenuation of ileal mucosal acidosi s was possibly caused by a different pattern of blood flow redistribution c ompared with L-NMMA.