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人因烧伤相关损伤住院，其中6，400至11，200人严重烧伤，烧伤面积至少占人体总表面积（BSA）的20%。二十年前，烧伤覆盖一个人的BSA的一半是致命的。然而，由于医学的进步，90% BSA烧伤的患者现在可以在这些损伤中幸存下来。严重烧伤会损伤皮肤，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类在体力消耗和/或高热暴露期间适当调节内部温度的关键反应。然而，主要研究者和其他人的发现表明，无论移植物成熟与否，移植皮肤的血管舒张和出汗反应都会受损或不存在。因此，具有大面积移植皮肤的患者可能具有降低的热耐受性。这个重要的问题尚未得到充分解决，因为它仍然是未知的程度皮肤移植损害内部温度的调节，或是否从非受伤的皮肤血管扩张和出汗反应提高可以补偿移植皮肤散热能力的降低。因此，本项目的第一个目的是检验以下假设：与非移植受试者相比，具有20-35% BSA移植皮肤的受试者将具有正常的体温调节反应，具有40-55% BSA移植皮肤的受试者将具有中度受损的体温调节反应，并且具有>60% BSA移植皮肤的受试者将具有严重受损的体温调节反应。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，从而降低其热相关损伤的风险。热适应是一种被广泛接受的改善需要工作的个体的温度调节的方法（即，消防员或军事人员），或选择在热环境条件下锻炼的人。这可能是热适应是有效的，以改善个人的温度调节皮肤移植超过他们的身体的大部分。为此，本项目的第二个目标是测试热适应改善具有不同BSA移植皮肤的个体的温度调节的假设。将使用新技术来评估体温调节传出变量的中枢和外周控制，以寻求所提出问题以及相关机制的答案。这项工作将进行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，患者和军方有价值，以了解严重烧伤和随后的皮肤移植对人体温度调节的影响，以及热适应是否会使这些人更好地耐受高温挑战，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和出汗的能力受损，因此身体大部分具有移植皮肤的个体可能具有受损的温度调节能力;尽管这尚未得到证实。该提案的总体目标是确定皮肤移植损害温度调节的程度，并调查热适应是否改善温度调节。从拟议的研究中获得的信息将对临床医生，患者和军方有价值，以了解严重烧伤和随后的移植对人体温度调节的影响，以及热适应是否会使这些人更好地耐受高热挑战，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.