Control of skin blood flow and sweating in grafted skin

描述（由申请人提供）：皮肤血流量和出汗增加是人体在运动和/或高温暴露时适当调节内部温度的关键反应。伤口，如烧伤，会损伤皮肤，需要切除受损组织并随后进行皮肤移植。尽管移植的皮肤最终会重建血管，但尚不清楚这种血管床是否会分别在低温和高温条件下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，与未烧伤的人相比，烧伤愈合超过40%的人在高温刺激时直肠温度更高，这表明烧伤受试者的热调节反应受损。然而，在这些研究中，没有控制是否进行皮肤移植，以及伤口/移植物的成熟度。鉴于缺乏关于皮肤移植对移植皮肤的血管重建和神经再生的短期和长期影响的信息，本提案的主要目的是验证人类裂厚移植物中皮肤血流的自主和非自主控制最初受损但随着移植物成熟而恢复正常的假设；而无论移植物成熟度如何，出汗反应仍然受损。此外，由于供体部位的血管和汗管因皮肤采集而受到破坏，因此也将从这些部位评估皮肤血流量和出汗的控制。这些目标将通过进行一系列新颖的实验来评估不同成熟度的皮肤移植受试者（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）对皮肤血流量和出汗的神经和非神经控制。此外，在整个资助期间，将每年对移植后5-9个月组的个人进行重新评估。从拟议的研究中获得的信息对于临床医生和患者了解这种手术的短期和长期后果都是有价值的。此外，该信息将为新兴技术（即合成皮肤，培养皮肤，生长因子等）的反应提供一个基准，可以比较移植物区域的神经再生和血管重建。

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.