Brain Cooling Causes Attenuation of Cerebral Oxidative Stress, Systemic Inflammation, Activated Coagulation, and Tissue Ischemia/Injury During Heatstroke

Abstract

The purpose of the present study was to assess the therapeutic effect of hypothermic retrograde jugular vein flush (HRJVF) on heatstroke. HRJVF was accomplished by infusion of 4 degrees C isotonic sodium chloride solution via the external jugular vein (1.7 mL/100 g of body weight over 5 min). Immediately after the onset of heatstroke, anesthetized rats were divided into 2 major groups and given the following: 36 degrees C or 4 degrees C isotonic sodium chloride solution, i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. When the 36 degrees C saline-treated rats underwent heat exposure, their survival time values were found to be 23 to 28 min. Immediately after the onset of heatstroke, resuscitation with an i.v. dose of 4 degrees C saline significantly improved survival during heatstroke (208-252 min). All heat-stressed animals displayed systemic inflammation and activated coagulation, evidenced by increased tumor necrosis factor alpha, prothrombin time, activated partial thromboplastin time, and d-dimer, and decreased platelet count and protein C. Biochemical markers evidenced cellular ischemia and injury/dysfunction: plasma levels of blood urea nitrogen, creatinine, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and alkaline phosphatase; and striatal levels of glycerol, glutamate, and lactate/pyruvate; dihydroxy benzoic acid, lipid peroxidation, oxidized-form glutathione reduced-form glutathione, dopamine, and serotonin were all elevated during heatstroke. Core and brain temperatures and intracranial pressure were also increased during heatstroke. In contrast, the values of mean arterial pressure, cerebral perfusion pressure, and striatal levels of local blood flow, partial pressure of oxygen, superoxide dismutase, catalase, glutathione peroxidase, and glutathions reductase activities were all significantly lower during heatstroke. The circulatory dysfunction, systemic inflammation, hypercoagulable state, and cerebral oxidative stress, ischemia, and damage during heatstroke were all significantly suppressed by HRJVF. These findings demonstrate that brain cooling caused by HRJVF therapy may resuscitate persons who had a stroke by attenuating cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia/injury during heatstroke.

Hypobaric hypoxia preconditioning attenuates acute lung injury during high-altitude exposure in rats via up-regulating heat-shock protein 70

“…In a previous report [36], an increase in oxidative stress in the hippocampus, as detected by an increase in free radical production and NO levels, was observed in rat exposed to a simulated high altitude equivalent to 6100 m in an animal decompression chamber for 3-7 days. Our present results also showed that the non-HHP rats had an increase in free radical production and NO x level in the BALF after a simulated HAE of 6000 m (9.8 % O 2 at 0.47 ATA) for 24 h. 2,3-DHBA and NO x are two well-known markers of cellular oxidative damage markers [37,38]. Again, the HAEinduced oxidative damage in lungs was significantly reduced by HHP in rats.…”

Hyperthermic preconditioning severely accelerates neuronal damage in the gerbil ischemic hippocampal dentate gyrus via decreasing SODs expressions

“…We found in this study that SOD1 and SOD2 expressions in the (H + ischemia)-group were intensely decreased in the polymorphic layer after ischemiareperfusion compared with those in the (N + ischemia)-group. Indeed, when experimental animals are exposed to hyperthermic condition, the value of SODs in the brain significantly decreases while the extent of lipid peroxidation and the rate of superoxide radical generation are significantly elevated [38]. On the basis of these reports, we strongly suggest that SODs are significantly decreased by hyperthermia-mediated ischemia and the decreased SODs might lead to a significant increase in superoxide anion production that are closely related with neuronal damage/death after transient cerebral ischemia.…”

What's New in Shock, August 2006

“…Heat stroke in the rat produces systemic inflammation characterized by thrombocytopenia, D-dimer appearance, loss of protein C, and increased TNF production, as well as organ injury (16). Retrograde jugular vein infusion of cold saline improves survival and reduces the magnitude of the inflammatory response.…”