| The purpose of this investigation was to determine if oxidative stress contributes to negative clinical outcomes during whole body hyperthermia. Project I determined: (a) if radicals could be detected in whole blood collected from conscious animals, and (b) if hyperthermia increases vascular concentrations of radicals consistent; with oxidative stress in splanchnic tissues. Project II explored hypoxia-related mechanisms of radical production by determining the effects of whole body hyperthermia on: (a) femoral artery and portal venous blood chemistries, and (b) the concentration of hypoxic cells in liver and intestine. Project III determined if pharmacologically increasing systemic antioxidant capacity or antagonizing NOS enzyme activities alters: vascular radical production, tissue injury, splanchnic vascular endotoxin concentration, or heat tolerance.;In project I, portal blood contained the radicals: ceruloplasmin, semiquinone, heme-NO;Data from project II suggests heat stress increases splanchnic oxygen uptake and metabolic acid production. Hyperthermia also expanded the concentration of hypoxic cells in intestine and liver. In intestinal tissues, hypoxic label retention was elevated only in mucosal epithelial cells. Cellular hypoxic label retention progressively increased moving from base to tip of duodenal and jejunal microvilli. This effect was diminished in ileal and colonic tissues. Within hepatic tissues, cellular hypoxic label concentration was elevated in zones 2 and 3 hepatocytes and Kupffer cells. These effects were more prominent in lobi caudati versus lobi dexter.;Interpretation of data collected in project III suggests that: (a) whole body hyperthermia promotes oxidative stress, multiorgan injury, and multiorgan dysfunction, (b) pharmacologically elevating systemic antioxidant capacity decreases radical production, preserves splanchnic blood flow, improves cardiac function, protects splanchnic viscera from injury, and improves hear tolerance, (c) antagonizing xanthine oxidase enzyme activity mimics these effects and preserves selective permeability of the intestine to endotoxins, and (d) intact cNOS activity is essential for normal heat tolerance, while antagonizing iNOS enzyme activity increases heat tolerance. |
