MECHANISM OF CIRCULATORY INSUFFICIENCY IN HEAT STROKE

运动引起的热衰竭是第二个最常见的原因， 美国运动员因头部和脊柱受伤而死亡。 此外，典型的中暑在美国造成数百人死亡， 1987年热浪中的希腊。 这种疾病的病理生理学 疾病仍然是模糊的，但心血管疾病的突出作用， 系统是公认的。 在最近的一次关于热的国际研讨会上， 中风，建议开发动物模型， 专门研究流向肝脏，肾脏， 皮肤和中枢神经系统。 我们建立这样一个模式3年 根据我们目前的发现，我们假设高温 会导致心血管功能不全， 中风涉及内脏血管控制的选择性丧失。 这 提案继续关注血管控制的系统机制 并开始探索相关的组织机制。 我们的具体目标 是为了评估（a）如果内脏血管收缩在高温 大鼠在小肠中产生粘膜损伤，增加毛细血管 渗透性，并引起导致低血压的内毒素血症;（B） 生存能力，（c）心肺压力反射的作用，氧气 自由基，内毒素和神经体液机制介导的 高温期间内脏血管阻力的变化;以及（d） 训练和热习服对循环反应的影响 到体温过高 我们还计划确定 有助于内脏血管的体内微循环 并建立一个隔离的血管准备， 使我们能够确定（a）在什么温度下， （B）血管内皮在介导血管扩张中的作用， 热应激动物的内脏阻力降低，和（c） 如果受体对NE的敏感性被高温显著改变。 体内测量将包括肾脏、上级肠系膜和尾部 动脉血流量，平均动脉压，心率，核心体 温度，以及一阶、二阶和三阶的内部尺寸 肠血管系统内的小动脉。 体外测量 隔离血管将包括压力和尺寸分析， 有无内皮完整的血管 在特定 协议，我们还将测量交感神经活动，渗透压 反射系数和血浆中的内毒素水平。 的 这项研究的意义在于它有助于理解 引起中暑和休克综合征的基本机制 血容量不足。 因此，这项研究产生的信息 应用于许多临床问题。

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.