Mechanisms of Cardiac Function and Cerebral Vascular Control during Heat Stress

描述（由申请人提供）：个体经常暴露在内部温度升高的条件下，导致皮肤血管传导增加，并伴有大量的汗液流失。在这种情况下，血压控制受到损害是很常见的，表现为头晕、眩晕、站立时恶心或类似的重力压力，这可能导致晕厥和受伤的可能性很高。本提案的目的是确定在热应激期间导致直立性不耐受的血压控制减弱的机制。具体目的1：验证热应激期间中央血容量（以中心静脉压为指标）的恢复可以改善血压控制和直立耐受的假设。具体来说，我们将研究容积恢复对以下方面的影响：1)SV与肺毛细血管楔压（即Frank-Starling曲线）之间的关系，以及2)重力压力下左室舒张末期容积。具体目标2：研究热应激时直立挑战时脑血流量（CBF）减少的机制。具体而言，我们将研究：1)热和站立联合应激时中心静脉压和心输出量降低对CBF的作用；2)热应激时动脉二氧化碳张力（PaCO2）降低导致CBF减少的相对贡献；3)热应激对脑血管系统对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+通过右旋糖酐/生理盐水输注恢复CBV期间的心血管和血液动力学变量来实现。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，这将为那些治疗体内温度升高的人，特别是当这种情况伴随着出血性损伤时，提供见解。这些人可能是在环境温度升高的条件下作战的士兵（如中东），在气候温暖地区服役的消防员和警察，或任何其他事件（如车祸），其中一个人在大量出血的同时体内温度升高。

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.