Mechanisms of Cardiac Function and Cerebral Vascular Control during Heat Stress

描述(由申请人提供)：个人经常暴露在体内温度升高的条件下，这会导致皮肤血管传导性增加，并伴随着大量出汗的液体损失。在这种情况下，患者的血压控制通常会受到损害，表现为头晕、眩晕和站立时的恶心，或类似的重力应激源，这可能会导致晕厥和很大的受伤可能性。这项建议的目的是确定热应激期间血压控制减弱导致立位不耐受的机制。具体目标1：测试在热应激期间恢复中心血容量(以中心静脉压为指标)可改善血压控制和立位耐力的假设。具体地说，容量恢复对以下方面的影响：1)SV与肺毛细血管楔压的关系(即Frank-Starling曲线)；2)重力应激时的左室舒张末期容量。具体目标2：研究热应激时立位挑战时脑血流量(CBF)更大幅度减少的机制。具体地说，我们将研究：1)在热和立位联合应激期间中心静脉压和心输出量降低对脑血流量的作用，2)动脉二氧化碳分压降低(PaCO2)导致热应激期间观察到的脑血流量减少的相对贡献，以及3)热应激对脑血管对PaCO2变化的敏感性的影响。这些目标将通过评估1)常温、2)热应激和3)热应激+通过葡聚糖/生理盐水恢复CBV期间的心血管和血流动力学变量来实现。一些方案将使用下体负压来减少CBV，从而模拟出血状态。公共卫生相关性：获得的数据将提供有关热应激期间血压控制受损的重要信息。重要的是，这将为那些治疗体内温度升高的人提供洞察力，特别是当这种情况伴随着出血性损伤时。这些人可能是在环境温度升高的条件下作战的士兵(例如中东)、在气候较温暖地区服役的消防员和警察，或任何其他个人在体内温度升高的同时大量流血的事件(例如车祸)。

DESCRIPTION (provided by applicant): Individuals are frequently exposed to conditions that elevate internal temperature which results in increased cutaneous vascular conductance accompanied by significant fluid loss via sweating. It is common for individuals in this condition to have compromised blood pressure control evidenced by lightheadedness, vertigo, and nausea upon standing or similar gravitational stressors, which can lead to syncope and a high potential of injury. The objective of this proposal is to identify mechanisms responsible for attenuated blood pressure control leading to orthostatic intolerance during heat stress. Specific Aim 1: Tests the hypothesis that restoration of central blood volume (indexed by central venous pressure) during heat stress improves blood pressure control and orthostatic tolerance. Specifically the effects of volume restoration on: 1) the relationship between SV and pulmonary capillary wedge pressure (i.e., Frank-Starling curve), and 2) left ventricular end diastolic volume during gravitational stress, will be examined. Specific aim 2: Examine mechanisms of greater reductions in cerebral blood flow (CBF) during an orthostatic challenge while heat stressed. Specifically we will examine: 1) the role of decreased central venous pressure and cardiac output during combined heat and orthostatic stress on CBF, 2) the relative contributions of reduced arterial CO2 tensions (PaCO2) causing reduced CBF observed during heat stress and 3) the effect of heat stress on the sensitivity of the cerebral vasculature to changes in PaCO2 . These objectives will be accomplished by evaluating cardiovascular and hemodynamic variables during 1) normothermia, 2) heat stress, and 3) during heat stress + restoration of CBV via dextran/saline infusion. Some protocols will use lower body negative pressure to reduce CBV and thus mimic a state of hemorrhage. PUBLIC HEALTH RELEVANCE: Data obtained will provide important information regarding compromised blood pressure control during heat stress. Importantly, this will provide insight to those who treat individuals with an elevated internal temperature and particularly when this scenario is accompanied with a hemorrhagic injury. Such individuals may be soldiers fighting in conditions in which environmental temperature is elevated (e.g. Middle East), firefighters and police officers who serve in warmer climate locations, or any other incidents (e.g., car accident) in which an individual is profusely bleeding while at the same time their internal temperature is elevated.