Control of skin blood flow and sweating in grafted skin

描述（由申请人提供）：每年有40,000至70,000人因烧伤住院，其中6,400至11,200人严重烧伤，烧伤面积至少占人体表面积（BSA）的20%。20年前，烧伤覆盖半个人的BSA是致命的。然而，由于医学的进步，90%牛血清白蛋白烧伤的患者现在都能存活。严重的烧伤会损伤皮肤，在许多情况下，需要切除受损组织并随后进行皮肤移植。皮肤血流量和出汗的增加是人体在体力消耗和/或高温暴露时适当调节体内温度的关键反应。然而，主要研究者和其他人的研究结果表明，无论移植皮肤的成熟度如何，移植皮肤的血管舒张和排汗反应都受损或缺失。因此，大面积植皮患者的热耐受性可能降低。这个重要的问题还没有得到充分的解决，因为它仍然不清楚皮肤移植在多大程度上损害了内部温度的调节，或者非受伤皮肤的血管舒张和出汗反应的增强是否可以补偿移植皮肤散热能力的降低。因此，本项目的第一个目标是验证以下假设：与未移植的受试者相比，移植20-35% BSA皮肤的受试者体温调节反应正常，移植40-55% BSA皮肤的受试者体温调节反应中度受损，移植bbb60 % BSA皮肤的受试者体温调节反应严重受损。目前尚不清楚具有大量BSA移植皮肤的个体是否能够适应高温气候，从而降低热相关损伤的风险。热适应是一种被广泛接受的方法，用于改善需要在炎热环境条件下工作的个人（即消防员或军事人员）或选择锻炼的人的温度调节。这可能是热适应是有效的，以改善温度调节的个体皮肤移植在他们的身体的大部分。为此，本项目的第二个目标是验证热驯化改善移植皮肤不同BSA个体的温度调节的假设。对提出的问题的答案，以及相关的机制，将采用新的技术来评估热调节传出变量的中枢和外周控制。进行这项工作的学术环境是独一无二的，因为治疗皮肤移植患者的外科医生和康复医生将与调查生理学家合作来解决这些重要问题。从拟议的研究中获得的信息将对临床医生、患者和军队有价值，有助于了解严重烧伤和随后的皮肤移植对人体温度调节的影响，以及热适应是否能让这些人更好地忍受高温挑战，从而提高热安全性和舒适性。公共卫生相关性：移植皮肤增加皮肤血流量和出汗的能力受损，因此身体大部分植皮的个体可能会降低温度调节能力；虽然这还没有得到证实。该提案的总体目标是确定皮肤移植损害温度调节的程度，并调查热驯化是否改善温度调节。从拟议的研究中获得的信息将对临床医生、患者和军队有价值，有助于了解严重烧伤和随后的移植对人体温度调节的影响，以及热适应是否能让这些人更好地忍受高温挑战，从而提高热安全性和舒适性。

DESCRIPTION (provided by applicant): Each year 40,000 to 70,000 individuals are hospitalized for burn related injuries, and of this number between 6,400 and 11,200 have severe burns covering at least 20% of the person's total body surface area (BSA). Twenty years ago burns covering half of a person's BSA were fatal. However, due to medical advances, patients with 90% BSA burned are now surviving these injuries Serious burns damage the skin, requiring, in many cases, excising the damaged tissue and subsequent skin grafting. Increases in skin blood flow and sweating are critical responses for humans to appropriately regulate internal temperature during physical exertion and/or hyperthermic exposure. However, findings from the principal investigator and others show that vasodilatory and sweating responses in grafted skin are impaired or absent regardless of the maturity of the graft. Thus, patients with large areas of grafted skin may have reduced thermal tolerance. This important question has not been adequately addressed as it remains unknown to what extent skin grafting impairs the regulation of internal temperature, or whether heightened vasodilator and sweating responses from non-injured skin can compensate for reduced heat dissipating capacity of grafted skin. Thus, the first objective of this project is to test the hypothesis that subjects with 20-35% of BSA grafted skin will have normal thermoregulatory responses, subjects with 40-55% BSA grafted skin will have moderately impaired thermoregulatory responses, and subjects with >60% BSA grafted skin will have severely impaired thermoregulatory responses when compared to non-grafted subjects. It is unknown whether individuals with substantial BSA of grafted skin can adapt to elevated temperature climates and thereby reduce their risk of a heat-related injury. Heat acclimation is a widely accepted approach to improve temperature regulation in individuals required to work (i.e., firefighters or military personnel), or who choose to exercise, in hot environmental conditions. It may be that heat acclimation is effective in improving temperature regulation of individuals with skin grafts over large portions of their body. To this end, the second objective of this project is to test the hypothesis that heat acclimation improves temperature regulation of individuals with varying BSA of grafted skin. Answers to the proposed questions, as well as related mechanisms, will be pursued using novel techniques to assess both central and peripheral control of thermoregulatory efferent variables. The academic environment in which this work will be conducted is unique in that surgeons and rehabilitation physicians, who treat skin graft patients, will collaborate with investigative physiologists to address these important questions. The information gained from the proposed studies will be valuable to clinicians, patients, and the military towards an understanding of the effects of serious burn injuries and subsequent skin grafting on human temperature regulation, and whether heat acclimation will allow these individuals to better tolerate a hyperthermic challenge and thus improve thermal safety and comfort. PUBLIC HEALTH RELEVANCE: Grafted skin has impaired capability to increase skin blood flow and sweating and thus individuals with a large portion of their body having grafted skin may have compromised temperature regulatory capacity; although this has not been confirmed. The overall objectives of the proposal are to identify the extent by which skin grafting impairs temperature regulation and to investigate whether heat acclimation improves temperature regulation. The information gained from the proposed studies will be valuable to clinicians, patients, and the military towards an understanding of the effects of serious burn injuries and subsequent grafting on human temperature regulation, and whether heat acclimation will allow these individuals to better tolerate a hyperthermic challenge and thus improve thermal safety and comfort.