Control of skin blood flow and sweating in grafted skin

描述(申请人提供)：皮肤血流量增加和出汗是人体在运动和/或高温暴露期间适当调节体内温度的关键反应。烧伤等伤口可能会损害皮肤，需要移除受损组织并随后进行皮肤移植。尽管移植的皮肤最终会血运重建，但目前尚不清楚这种血管床是否会在低温和高温条件下分别通过皮肤血管收缩和血管扩张来控制体内温度。事实上，有限数量的研究表明，烧伤愈合超过40%的人在高温挑战中的直肠温度高于未烧伤的同龄人，这表明烧伤对象的热调节反应受损。然而，在这些研究中，皮肤移植的存在或不存在，以及伤口/移植的成熟度都没有得到控制。由于缺乏关于皮肤移植对移植皮肤血运重建和神经再支配的短期和长期影响的信息，本建议的主要目的是检验这样一种假设，即人体中厚移植物对皮肤血流的自主和非自主控制最初受到损害，但随着移植物的成熟而恢复正常；而出汗反应仍然受损，无论移植物的成熟度如何。此外，由于供体部位的血管和汗管因皮肤采集而中断，因此也将从这些部位评估皮肤血液流动和出汗的控制情况。这些目标将通过实施一系列新的实验来实现，以评估神经和非神经对不同成熟度的中厚皮片移植受者皮肤血流和出汗的控制(即，在参与研究前5-9个月、26-38个月、50-62个月和72-86个月进行移植手术)。此外，移植后5-9个月组的个人将在整个资助期内每年进行重新评估。从拟议的研究中获得的信息将对临床医生和患者都有价值，有助于了解这种外科手术的短期和长期后果。此外，这些信息将提供一个基准，可以将新兴技术(如人造皮肤、培养皮肤、生长因子等)引起的反应与移植区域的神经再支配和血运重建进行比较。

DESCRIPTION (provided by applicant): Increases in skin blood flow and sweating are critical responses for humans to appropriately regulate internal temperature during exercise and/or hyperthermic exposure. Wounds, such as burns, can damage the skin requiring removal of the damaged tissue and subsequent skin grafting. Although grafted skin ultimately becomes revascularized, it remains unclear whether this vascular bed will ever contribute to the control of internal temperature through cutaneous vasoconstriction and vasodilation during hypothermic and hyperthermic conditions, respectively. In fact, a limited number of studies showed that individuals with healed burns over 40% of their body had higher rectal temperatures during a hyperthermic challenge relative to non-burned counterparts, suggesting impaired thermal regulatory responses of the burned subjects. However, in those studies the presence or absence of skin grafting, as well as the maturity of the wound/graft, was not controlled. Given the lack of information regarding short and long term consequences of skin grafting with respect to revascularization and reinnervation of the grafted skin, the primary objective of this proposal is to test the hypothesis that autonomic and non-autonomic control of skin blood flow in human split-thickness grafts are initially impaired but return towards normal as the graft matures; while sweating responses remain impaired regardless of graft maturity. Moreover, since the vasculature and sweat ducts of donor sites are disrupted due to skin harvesting, the control of skin blood flow and sweating will also be assessed from these sites. These objectives will be accomplished by performing a series of novel experiments to assess neural and non-neural control of skin blood flow and sweating from subjects with split-thickness skin grafts of varying maturities (i.e. graft procedure performed 5-9, 26-38, 50-62, and 72-86 months prior to study participation). In addition, individuals in the 5-9 month post-graft group will be reassessed yearly throughout the funding period. The information gained from the proposed studies will be valuable to both clinicians and patients towards an understanding of the short and long-term consequences of this surgical procedure. Moreover, this information will provide a benchmark from which responses due to emerging technologies (i.e. synthetic skin, cultured skin, growth factors, etc) could be compared with respect to reinnervation and revascularization of the grafted area.