HYPERTHERMIA PROMOTES SPLANCHNIC ENDOTOXEMIA AND NOS II INDUCTION IN THE SMALL INTESTINE 1070

Acute heat stress increases splanchnic vascular concentrations of NO* and radical species consistent with oxidative stress in splanchnic tissues. We hypothesize that acute heat stress compromises intestinal barrier function, promoting translocation of bacterial endotoxins from the gut to the splanchnic circulation. Using exogenous SOD supplementation, NO* inhibitors, L-argininc supplementation, and the xanthine oxidase inhibitor allopurinol, this study focused on the effects of acute heat stress on splanchnic reactive oxygen species generation, intestinal barrier function and splanchnic endotoxemia. In anesthetized rats fitted with portal venous catheters and exposed to a temperature of 40°C, we sampled blood as colonic temperature (Tc) rose from 37°C to 43.5°C. Portal venous endotoxin concentrations in control samples collected from rats prior to heat exposure were 28±7 pg/ml. At 41.5°C, endotoxin concentration increased to 62±4 pg/ml in saline-injected controls. This was associated with marked induction of NOS II in the small intestine 2h post heat stress. The NOS I inhibitor L-NAME (25-125 μM) significantly increased portal venous endotoxin concentration to 78±4 pg/ml. L-arginine (100 - 300 μM), SOD (10-30 mg/kg), and the NOS II inhibitor aminoguanidine (25-100μM), did not effect 41.5°C endotoxin values. Allopurinol (300 μM) significantly decreased 41.5°C portal venous endotoxin concentration to 37°C control values (29±8 pg/ml). These results suggest that xanthine oxidase-derived reactive oxygen species increase intestinal permeability during acute heat stress, and that NOS I activity is necessary to protect intestinal barrier function.