Hydroxyethyl Starch Produces Attenuation of Circulatory Shock and Cerebral Ischemia During Heatstroke

Abstract

We hypothesized that hydroxyethyl starch (HES), which maintains colloid osmotic pressure and potentially "seals" capillary leaks, would ameliorate circulatory shock and cerebral ischemia during heatstroke in a rat model. Animals under urethane anesthesia were exposed to high ambient temperature (Ta) of 42 degrees C until mean arterial pressure and local cerebral blood flow in the striatum began to decrease from peak level, which was arbitrarily defined as the onset of heatstroke. Control rats were exposed to 24 degrees C. In rats treated with 1 mL/kg, 11 mL/kg, or 22 mL/kg of normal saline (NS) immediately after the onset of heatstroke, the values for survival time (interval between the initiation of heatstroke and animal death) were found to be 21 +/- 2, 36 +/- 9, or 92 +/- 7 min, respectively. Intravenous administration of 11 mL/kg of HES (about 5 times the volume-expanding effect of 11 mL/kg of NS), but not 2 mL/kg of HES (about the same volume-expanding effect as 11 mL/kg NS), significantly increased the survival time from the control values of 36 +/- 9 min to new values of 181 +/- 13 min. In NS (11 mL/kg)-treated or HES (2 mL/kg)-treated rats after heatstroke onset, the values for mean arterial pressure, stroke volume, total peripheral resistance, cerebral blood flow, blood pH, Paco2, Pao2, and brain Po2 were significantly lower than those of rats kept at Ta 24 degrees C. In contrast, the values for colonic temperature and the extracellular concentrations of glutamate, glycerol, and lactate/pyruvate ratio obtained in striatum were significantly higher than those of controls. The heatstroke-induced arterial hypotension, decreased stroke volume and total peripheral resistance, decreased blood pH and Pao2, decreased brain Po2, and increased levels of striatal glutamate, glycerol, and lactate/pyruvate ratio in NS-treated rats were all attenuated significantly by increasing the volume expansion with 11 mL/kg of HES administered immediately at the onset of heatstroke. Our data suggest that HES therapy seems superior to NS treatment during heatstroke. The benefit of HES therapy during heatstroke might have something to do with volume expansion rather than capillary permeability.

Chinese Herbal Medicine, Shengmai San, Is Effective for Improving Circulatory Shock and Oxidative Damage in the Brain During Heatstroke

“…When rodents are exposed to external heat stress, they have both decreased stroke volume and decreased peripheral vascular resistance produced arterial hypotension (28). Both arterial hypotension and intracranial hypertension eventually led to cerebral hypoperfusion and hypoxia after the onset of heatstroke, as demonstrated in the present results.…”

Effects of Combination Treatment with Dexamethasone and Mannitol on Neuronal Damage and Survival in Experimental Heat Stroke

“…24,25,27) Excessive accumulation of glutamate has been shown in ischemic brain tissue. 28,29) Indeed, both present and previous results 7,37) have demonstrated that extracellular levels of glutamate, glycerol and lactate/pyruvate in ischemic brain are greater in heat stroke rats compared with those of normothermic controls. Meanwhile, evidences of histopathological morphology and neuronal damage score also reveal severe neuronal damage (shown in Fig.…”

“…22,35,36) There is evidence that cerebral ischemia (due to arterial hypotension and intracranial hypertension) may be one of the major causes to induce further damage after heat stroke onset. 14,19,37) After heat stroke induction, the CBF is instantly drops from highest peak, and it is concomitant with significant increments of cerebral ischemia and injury indexes, as shown in Fig. 1.…”

“…[40][41][42] As for heat stroke in our previous studies, the plasma levels of TNF-a were greatly elevated during heat stroke in rats. 37) The increased levels of the inflammatory cytokines in the peripheral blood stream were showed to be well related to the severity of heat stroke. 13,43) Hence, the plasma levels of TNF-a in heat stroke rats are also observed in this study.…”

Selective Inhibition of Inducible Nitric Oxide Synthase Attenuates Renal Ischemia and Damage in Experimental Heatstroke

“…Overproduction of NO may contribute to the splanchnic vasodilation that precedes vascular collapses with heatstroke. Our previous results have further shown that in addition to overproduction of NOx in brain, decreased cardiac output (due to decreased total peripheral vascular resistance and stroke volume), intracranial hypertension, and cerebral ischemia and hypoxia, and hyperthermia occur during heatstroke in the rat (10,11,21). Our previous findings have also shown that accumulation of large amounts of reactive oxygen species in various organs including the kidney and the brain is associated with hyperthermia, arterial hypotension, and cerebral ischemia and injury during heatstroke (22,23).…”