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人因烧伤而住院，其中6,400至11,200人被严重烧伤，烧伤面积至少占人体总表面积的20%。20年前，烧伤覆盖了一个人一半的BSA是致命的。然而，由于医学的进步，90%BSA烧伤的患者现在正在这些创伤中存活下来，严重烧伤损害了皮肤，在许多情况下，需要切除受损组织并随后进行皮肤移植。皮肤血流量增加和出汗是人体在体力消耗和/或高温暴露期间适当调节体内温度的关键反应。然而，首席研究人员和其他研究人员的发现表明，无论移植皮肤的成熟度如何，移植皮肤的血管扩张和出汗反应都会受损或消失。因此，大面积皮肤移植的患者可能会降低耐热性。这个重要的问题还没有得到充分的解决，因为尚不清楚皮肤移植在多大程度上损害了体内温度的调节，也不知道非损伤皮肤的血管扩张剂和出汗反应是否可以弥补移植皮肤散热能力的下降。因此，该项目的第一个目标是测试这样一种假设：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60%BSA皮肤的受试者与未移植皮肤的受试者相比，体温调节反应严重受损。目前尚不清楚移植皮肤有大量BSA的个体是否能够适应高温气候，从而降低他们与热有关的伤害的风险。热适应是一种被广泛接受的方法，可以在炎热的环境条件下改善需要工作的个人(即消防员或军事人员)或选择锻炼的人的温度调节。这可能是热习服有效地改善了身体大部分部位皮肤移植的个体的体温调节。为此，该项目的第二个目标是测试热习服改善移植皮肤BSA不同的个体的温度调节这一假设。将使用新的技术来评估体温调节传出变量的中枢和外周控制，以寻求对拟议问题的答案以及相关的机制。进行这项工作的学术环境是独特的，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，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，以及热习服是否会使这些人更好地耐受高温挑战，从而改善热安全性和舒适性。公共卫生相关性：移植的皮肤会损害增加皮肤血流量和出汗的能力，因此身体很大一部分人移植的皮肤可能会损害体温调节能力；尽管这一点尚未得到证实。该提案的总体目标是确定皮肤移植损害温度调节的程度，并调查热习服是否改善了温度调节。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，有助于了解严重烧伤和随后的移植物对人体温度调节的影响，以及热习服是否会使这些人更好地耐受高温挑战，从而改善热安全性和舒适性。

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.