Therapeutic evaluation of several substances in a rat heatstroke model

• Main Authors: Cheng-Kuei Chang, 張丞圭
• Other Authors: Mao-Tsun Lin, Ph. D.
• Format: Others
• Language: zh-TW
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/35176879539978864630

博士 === 國立陽明大學 === 生理學研究所 === 89 === Patients with heatstroke display hyperthermia, neurological abnormalities and multiple organ disorders. Previously, we have exposed the animal to a hot environment (42℃) to induce heatstroke, showing cerebral dopamine, serotonin and glutamate overload, and ischemic injury resulting from intracranial hypertension and arterial hypotension are responsible for occurrence of central nervous system, syndromes associated with heatstroke. No pharmacological agent has been found to be beneficial in the treatment of heatstroke. Therefore, in the present study, we attempted to test the therapeutic potentials of hypervolemic hemodilution, dl-tetrahydropalmatine and nimodipine treatment in a rat heatstroke model. Hypervolemic hemodilution was produced by intravenous administration of 10% human albumin. Relative and absolute blood flow in the corpus striatum were determined using the laser Doppler flowmetry and the autoradiography diffusible tracer technique, respectively. The dopamine release in the striatum was estimated using the in vivo microdialysis technique. After onset of heatstroke, animals with hypervolemic state alone, produced by saline or heparinized blood injection, displayed higher values of dopamine release, as well as neuronal damage score in the striatum, hypothalamus, or cortex, but lower values of mean arterial pressure and blood flow in the striatum, hypothalamus, or cortex compared to normothermic contrals. However, the heatstroke-induced arterial hypotension, cerebral ischemia, increases striatal dopamine overload, and increased neuronal damage score were attenuated by induction of both hypervolemic and hemodilution state with 10% albumin either before or after the onset of heatstroke. In addition, constant infusions of a vasopressor agent phenylephrine (2 mg kg-1 min-1) after the onset of heatstroke failed to maintain appropriate levels of mean arterial pressure and resulted in no protection against heatstroke. Thus, it appears that the observed benefit of the 10% albumin is secondary to hemodilution and/or maintenance of mean arterial pressure. Corydalis, is recognized as a safe and often effective remedy for abdominal pain by practitioners of Chinese herbal medicine. DL-Tetrahydropalmatine, an active principle isolated from corydalis, possesses analgesic, sedative, hypnotic and antihypertensive effects. In the present results, the heatstroke-induced hyperthermia, arterial hypotension, cerebral ischemia, brain monoamine overload, and cerebral neuronal injury were attenuated by pretreatment with dl— tetrahydropalmatine. The data indicate that dl-tetrahydropalmatine provides neuroprotective effect in heatstroke. Nimodipine, the active ingredient of Nimotop, has a predilective cerebral antivasoconstrictive and antiischemic activity. Vasoconstriction provoked in vitro by various vasoactive substances or by blood and blood degradation products can be prevented or eliminated by nimodipine. In the present study, both the latency of heatstroke onset (interval between the start of heat exposure and the onset of heatstroke) and survival time (interval between the onset of heatstroke and cardiac arrest) were defined. It was found that both hypervolemic hemodilution and dl-tetrahydropalmatine, although having no effect on the latency of heatstroke onset, prolonged the survival time in rats with heatstoke. In contrast, both the latency of heatstroke onset and the survival time were all attenuated by nimodipine treatment. It seems that nimodipine impair the resistance of rats in the heat. In conclusion, the present results suggest that hypervolemic hemodilution (produced by intravenous infusions of 10% albumin) and/or dl-tetrahydropalmatine are beneficial in the treatment of heatstroke in a rat model.