Mechanisms of Cardiac Function and Cerebral Vascular Control during Heat Stress

描述（由申请人提供）：个人经常暴露于内部温度升高的条件下，导致皮肤血管传导增加，伴随着通过出汗造成的大量体液流失。这种情况下的个体通常会出现血压控制受损，表现为站立或类似重力应激时的头晕、眩晕和恶心，这可能导致晕厥和高度损伤。本提案的目的是确定机制负责衰减血压控制导致直立性不耐受在热应激。具体目标1：测试热应激过程中中心血容量（以中心静脉压为指标）恢复可改善血压控制和立位耐力的假设。特别是容量恢复对以下方面的影响：1）SV和肺毛细血管楔压之间的关系（即，Frank-Starling曲线），和2）重力应力期间左心室舒张末期容积。具体目标2：检查热应激时直立挑战期间脑血流量（CBF）更大减少的机制。具体来说，我们将检查：1）热应激和直立性应激联合作用期间中心静脉压和心输出量降低对CBF的作用，2）热应激期间观察到的导致CBF降低的动脉CO2张力（PaCO 2）降低的相对贡献，3）热应激对脑血管系统对PaCO 2变化的敏感性的影响。这些目标将通过评价1）常温、2）热应激和3）热应激+通过右旋糖酐/生理盐水输注恢复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降低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，这将为那些治疗内部温度升高的个体的人提供见解，特别是当这种情况伴有出血性损伤时。这样的个人可以是在环境温度升高的条件下作战的士兵（例如，中东）、在较温暖的气候位置服务的消防员和警察、或任何其他事件（例如，车祸），其中一个人大量出血，同时他们的内部温度升高。

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.