MECHANISM OF CIRCULATORY INSUFFICIENCY IN HEAT STROKE

劳累引起的热衰竭是第二常见的原因 death following head and spinal injuries among American athletes. Moreover, classical heat stroke killed hundreds of people in the USA and 1987 年热浪期间的希腊。这一现象的病理生理学 这种疾病仍然不清楚，但心血管疾病的卓越作用 system is well recognized. At a recent international workshop on heat 建议开发中风动物模型 特别研究肝脏、肾脏的血流分布， skin, and CNS during hyperthermia. We established such a model 3 years ago and based on our current findings we hypothesize that hyperthermia 导致心血管功能不全，而热量的致命机制 中风涉及内脏血管控制的选择性丧失。 这个 提案继续关注血管控制的系统机制 并开始探索所涉及的组织机制。 我们的具体目标 评估 (a) 热疗中内脏血管是否收缩 大鼠小肠粘膜损伤，毛细血管扩张 渗透性，并引起内毒素血症，导致低血压； (二) survivability, (c) the role of cardiopulmonary baroreflexes, oxygen 自由基、内毒素和介导的神经体液机制 热疗期间内脏血管阻力的变化；和（四） the effects of training and heat acclimation on the circulatory response 至高热。 We also plan to identify the vessels within the 体内微循环有助于内脏血管 阻力并建立隔离容器准备， 使我们能够确定 (a) 容器在什么温度下的电阻 dilate, (b) the role of the vascular endothelium in mediating the 热应激动物的内脏抵抗力降低，以及（c） if receptor sensitivity to NE is significantly altered by hyperthermia. In vivo measurements will include renal, superior mesenteric, and caudal 动脉血流量、平均动脉压、心率、核心体 温度和一阶、二阶和三阶内部尺寸 arterioles within the intestinal vasculature. 体外测量 isolated vessels will include pressure and dimensional analysis on 内皮完整或不完整的血管。 具体来说 protocols, we will also measure sympathetic nerve activity, the osmotic reflection coefficient, and endotoxins levels in the plasma. 的 这项研究的意义在于它有助于理解 basic mechanisms underlying heat stroke and shock syndromes produced by 血容量不足。 Thus, the information generated by this research has application to numerous clinical problems.

Exertion induced heat exhaustion is the second most common cause of death following head and spinal injuries among American athletes. Moreover, classical heat stroke killed hundreds of people in the USA and Greece during the heat waves of 1987. The pathophysiology of this disorder remains obscure, but the preeminent role of the cardiovascular system is well recognized. At a recent international workshop on heat stroke it was recommended that animal models be developed to specifically investigate blood flow distribution to the liver, kidney, skin, and CNS during hyperthermia. We established such a model 3 years ago and based on our current findings we hypothesize that hyperthermia causes cardiovascular insufficiency and that the fatal mechanism in heat stroke involves the selective loss of splanchnic vascular control. This proposal continues to focus on systemic mechanisms of vascular control and begins to explore the tissue mechanisms involved. Our specific aims are to evaluate (a) if splanchnic vasoconstriction in the hyperthermic rat produces mucosal lesions in the small intestine, increases capillary permeability, and causes endotoxemia leading to hypotension; (b) survivability, (c) the role of cardiopulmonary baroreflexes, oxygen radicals, endotoxins, and neurohumoral mechanisms in mediating the changes in splanchnic vascular resistance during hyperthermia; and (d) the effects of training and heat acclimation on the circulatory response to hyperthermia. We also plan to identify the vessels within the microcirculation, in vivo, that contribute to splanchnic vascular resistance and to establish an isolated vessel preparation that will enable us to determine (a) at what temperature resistance vessels dilate, (b) the role of the vascular endothelium in mediating the reduction in splanchnic resistance in the heat-stressed animal, and (c) if receptor sensitivity to NE is significantly altered by hyperthermia. In vivo measurements will include renal, superior mesenteric, and caudal artery blood flows, mean arterial pressure, heart rate, core body temperature, and internal dimensions of 1st, 2nd, and 3rd order arterioles within the intestinal vasculature. In vitro measurements on isolated vessels will include pressure and dimensional analysis on vessels with and without their endothelium intact. In specific protocols, we will also measure sympathetic nerve activity, the osmotic reflection coefficient, and endotoxins levels in the plasma. The significance of this research lies in its contribution to understanding basic mechanisms underlying heat stroke and shock syndromes produced by hypovolemia. Thus, the information generated by this research has application to numerous clinical problems.