The mechanisms underlie the hypothermia therapy in experimental heatstroke

• Main Authors: Yueh -Ting Chou, 周岳廷
• Other Authors: Mao Tsun Lin
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/29083912645089881825

博士 === 國立陽明大學 === 生理學研究所 === 91 === Heatstroke develops at rest in a hot environment、physical work in warm environments or strenuous exercise in other than cold environments. In general, the symptoms of heatstroke are (a) hyperthermia, (b) multiple organ failure, and (c) neural dysfunction. The good efficient treatment of heatstroke is cooling. The present study attempted to ascertain the possible mechanisms underlie the hypothermia therapy in experimental heatstroke. The present study used a well-characterized experimental heatstroke model. Animals under urethane anesthesia were exposed to water blanket temperature (Tblanket) of 42℃ until mean arterial pressure (MAP) and regional cerebral blood flow (CBF) began to decrease from their peak levels, which was arbitrarily defined as the onset of heatstroke. Control animals were exposed to 26℃. Cooling was accomplished by decreasing Tblanket from 42℃ to 16℃. The following parameters were assessed：1. colonic temperature (Tco)、mean arterial pressure (MAP)、heart rate (HR)、and cerebral blood flow (CBF). 2. The arterial blood gas including： PaO2、PaCO2、pH、lactate and glucose；3. The extracellular levels of glutamate (a cellular ischemia marker), dopamine、glycerol (a cellular injury marker), lactate / pyruvate ratio (a cellular ischemia marker ) and glucose in brain；and 4. cerebral tissue O2 contents、intracranial pressure (ICP) and brain temperature. In addition, the present study used noninvasive methods including both MRI and PET to monitor brain functional alteration in experimental heatstroke. Relative cerebral volume (rCBV) and cerebral basal ganglia dopamine system was also assessed during heatstroke. The values of MAP、CBF、Tco、HR、PaO2、PaCO2、pH、and rCBV after the onset of heatstroke in heatstroke rats received no cooling were all significantly lower than those in control rats. On the other hand, the values of the arterial blood lactate、neuronal damage score、GFAP、extracellar ischemia and damage markers in the hippocampus、extracellular levels of dopamine in the striatum、basal ganglia / cerebellum FDOPA ratio in the striatum were all greater. Cooling immediately after the onset of heatstroke reduced the heatstroke-induced circulatory shock, tissue hypoxemia, lactacidemia, hyperthermia, neuronal damage, cerebral gliosis and cerebral ischemia, and surge of dopamine, basal ganglia / cerebellum FDOPA ratio, rCBV autoregulation failure in the striatum, and surge of cellular levels of ischemia, and injury markers in the hippocampus, and resulted in prolongation of the time to death (the interval between the start of heat stress and cardiac arrest). The mode of protective action of cooling is apparently multi-focal reactions in heat stroke animals, namely, suppressing (1) lactacidemia；(2) tissue acidification；(3) low oxygenation；(4) arterial hypotension (5) cerebral ischemia (6) surge of dopamine, glycerol, glutamate, and lactate / pyruvate in brain；(7) proliferation of glial cells (8) production of cerebral neuronal damage；and (9) cerebral autoregulation failure. In particular, cooling suppresses circulatory shock, cerebral ischemia and neuronal injury and and results in prolongation of survival in heat stroke animals.