Splanchnic tissues undergo hypoxic stress during whole body hyperthermia

Abstract

Exposure of conscious animals to environmental heat stress increases portal venous radical content. The nature of the observed heat stress-inducible radical molecules suggests that hyperthermia produces cellular hypoxic stress in liver and intestine. To investigate this hypothesis, conscious rats bearing in-dwelling portal venous and femoral artery catheters were exposed to normothermic or hyperthermic conditions. Blood gas levels were monitored during heat stress and for 24 h following heat exposure. Hyperthermia significantly increased arterial O2 saturation, splanchnic arterial-venous O2 difference, and venous[Formula: see text], while decreasing venous O2 saturation and venous pH. One hour after heat exposure, liver glycogen levels were decreased ∼20%. Two hours after heat exposure, the splanchnic arterial-venous O2 difference remained elevated in heat-stressed animals despite normal Tc. A second group of rats was exposed to similar conditions while receiving intra-arterial injections of the hypoxic cell marker [3H]misonidazole. Liver and intestine were biopsied, and [3H]misonidazole content was quantified. Heat stress increased tissue [3H]misonidazole retention 80% in the liver and 29% in the small intestine. Cellular [3H]misonidazole levels were significantly elevated in intestinal epithelial cells and liver zone 2 and 3 hepatocytes and Kupffer cells. This effect was most prominent in the proximal small intestine and small liver lobi. These data provide evidence that hyperthermia produces cellular hypoxia and metabolic stress in splanchnic tissues and suggest that cellular metabolic stress may contribute to radical generation during heat stress.

Effects of supplemental zinc amino acid complex on gut integrity in heat-stressed growing pigs

“…Interestingly, almost all aspects of intestinal integrity deteriorated from days 1 to 7 of HS (Table 2) and this suggests that acclimation (from a production perspective) is partially independent of HS-induced intestinal barrier dysfunction. Heat-stressed animals divert blood flow from the viscera to the periphery in an attempt to maximize heat dissipation (Lambert et al, 2002), which in addition to hyperthermia leads to intestinal hypoxia (Hall et al, 1999). Enterocytes are particularly sensitive to hypoxia and nutrient restriction (Rollwagen et al, 2006), resulting in ATP depletion, and increased oxidative and nitrosative stress (Hall et al, 2001).…”

Hsp-72, a candidate prognostic indicator of heatstroke

“…Although, this difference between in vitro and in vivo effects of heat shock is not entirely clear, it may be in part attributable to the importance of the interaction of the cells with their environment. Thermoregulation in acute heat stress induces redistribution of blood flow that may result in variable visceral perfusion (Hales et al 1979;Rowell 1983;Hall et al 1999) and storage of heat (Febbraio and Koukoulas 2000;Kuboki et al 2007;Dickson et al 1979) among regions and organs of the body, particularly the splanchnic organs. These could have accounted for the differential Hsp-72 expression noted in our study.…”

Aminoguanidine Protects Against Intracranial Hypertension and Cerebral Ischemic Injury in Experimental Heatstroke

“…In rats, heat stress leads to increased metabolic demand and reduced splanchnic blood flow, which in turn induce intestinal and hepatocellular hypoxia; the hypoxia results in the generation of highly reactive oxygen and nitrogen species that accelerate mucosal injury (1,2). Intestinal mucosal permeability to endotoxin increases in heat-stressed rats (3).…”