INCREASED ORGAN BLOOD-FLOW IN CHRONIC ENDOTOXEMIA IS REVERSED BY NITRIC-OXIDE SYNTHASE INHIBITION

We evaluated regional blood flows in a hyperdynamic sepsis model and the reversal of increased flows by blockade of nitric oxide (NO) synthase. Seven awake sheep were continuously infused with Escherichia coli endotoxin [lipopolysaccharide (LPS), 10 ng.kg(-1).min(-1)] for 48 h. The NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME, 25 mg/kg) was injected after 24 h. Blood flows to systemic organs were determined with the radioactive microsphere technique. LPS induced elevation of cardiac index by 36% (P < 0.05) and a fall in systemic vascular resistance index by 37% (P < 0.05) at 0 h [time of L-NAME administration, 24 h after infusion of LPS had begun]. L-NAME administration normalized cardiac index [6.1 +/- 0.5 at 4 h posttreatment, 6.1 +/- 0.51 min(-1).m(-2) at -24 h (baseline)] and systemic vascular resistance index (1,333 +/- 105 at 4 h posttreatment, 1,280 +/- 163 dyn.s.cm(-5) m(2) at -24 h) and reduced all regional blood flows to near-baseline levels for the remainder of the study period (24 h). O-2 consumption was unaffected by treatment.