Passive heating as an accessible and tolerable strategy to improve the inflammatory profile and cardiometabolic health in people with spinal cord injury

脊髓损伤后，瘦肌肉质量减少，植物神经功能紊乱，以及相关的身体机能下降。 缺乏活动（与身体健全的人群相比）会导致心血管疾病的发生 (CVD) 和 2 型糖尿病 (T2DM) 是发病率和死亡率的主要原因。1-3 越来越多的证据表明，以静息浓度升高为特征的慢性低度炎症 促炎细胞因子介导这种关系。4 SCI 患者体内的促炎细胞因子浓度升高 与健全 (AB) 个体相比，促炎标记物3,5 葡萄糖利用受损以及 受伤后 3-6 周内就会发生血管重塑。6,7 在身体健全 (AB) 人群中， 运动训练可以增加瘦体重，提高葡萄糖利用率，重要的是，还可以减少慢性病 低度炎症，可能是通过血浆白细胞介素 (IL)-6 浓度的急剧增加和 每次训练后都会产生抗炎细胞因子。10 虽然运动是一种具有成本效益的干预措施，可降低 由于 SCI 患者的身体能力下降，导致慢性疾病的风险增加，因此他们常常无法参与 与 AB 人相比，SCI 患者没有看到运动和运动的抗炎益处。有 越来越多的证据表明，急性（仅 1 次治疗）和慢性（4-8 次重复治疗） 周）被动加热可以减少 AB 人的炎症。患有 SCI 的人，急性（一 约 60 分钟的疗程）被动热疗可减少炎症，但只能持续很短的时间。影响发病率 和死亡率，需要长期减轻炎症，因此，慢性（即； 需要研究较长时间的被动热疗。这是第一个研究 调查慢性被动热疗对 SCI 患者的影响及其对 炎症、葡萄糖利用和内皮功能。我们假设六周的被动 热疗会减少炎症介质、葡萄糖利用率和内皮功能。 方法：10 名感觉运动完全性 (AIS A) SCI（C2-T6 级）患者将参加为期 8 周的活动 没有被动加热（对照 = CON），然后进行 8 周的被动热应激（干预 = INT），使用 电热毯 60 分钟，每周 2-3 次。炎症标志物（TLR4、Hsp70、CRP、IL-6、TNF-α、IL-1β、 IL-10）、口服葡萄糖耐量和皮肤血流随局部热增高（一氧化氮）的变化 相关）将在基线、CON 之后、INT 之后进行测量。预期结果：慢性被动 热应激会减少慢性炎症，提高葡萄糖利用率并改善内皮功能。 初步研究和未来方向：这项工作采用了一种可行且实用的被动方法 使用电热毯和水灌注服进行加热，这是 Dr. 开发的。 Trbovich 的实验室。11 该提案采取后续步骤收集试点数据，以研究潜在的治疗方法 这种实用的被动加热方法对 SCI 后发病和死亡主要原因的影响。

After spinal cord injury, the decrease in lean muscle mass, autonomic dysfunction, and relative physical inactivity (compared to the able-bodied population) contribute to the development of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) to be leading causes of morbidity and mortality.1-3 There is increasing evidence that chronic low-grade inflammation, characterised by elevated resting concentrations of pro-inflammatory cytokines, mediate this relationship.4 Persons with SCI have elevated concentrations of pro-inflammatory markers compared with able-bodied (AB) individuals,3,5 impaired glucose utilization and vascular remodelling that occurs as soon as 3-6 weeks post injury.6,7 In the able-bodied (AB) population, exercise training increases lean body mass, improves glucose utilization, and importantly, also reduces chronic low-grade inflammation, potentially via the acute increase in plasma concentrations of interleukin (IL)-6 and anti-inflammatory cytokines following each session.10 While exercise is a cost-effective intervention to lower the risk for chronic disease, the reduced physical capacity of people with SCI often precludes participation in exercise and anti-inflammatory benefits of exercise are not seen in SCI compared to AB persons. There is growing and emerging evidence that acute (1 session only) and chronic (repeated sessions over 4-8 weeks) passive heating can decrease inflammation in AB persons. In persons with SCI, acute (one ~60min session) passive heat therapy decreases inflammation, but for a short time only. To impact morbidity and mortality, long-term attenuation of inflammation will be required and thus, the impact of chronic (i.e.; repeated sessions) passive heat therapy over a longer time period needs to be studied. This is the first study to investigate the impact of chronic passive heat therapy in persons with SCI and its impact on inflammation, glucose utilization, and endothelial function. We hypothesize that six weeks of passive heat therapy will decrease inflammatory mediators, glucose utilization and endothelial function. Methods: Ten persons with sensorimotor complete (AIS A) SCI (levels C2-T6) will participate in 8 weeks without passive heating (control = CON) followed by 8 weeks of passive heat stress (intervention = INT) using electrical heating blankets for 60min 2-3x/week. Inflammatory markers (TLR4, Hsp70, CRP, IL-6, TNF-α,IL-1β, IL-10), oral glucose tolerance and skin blood flow changes with local thermal hypermia (nitric oxide dependent) will be measured at baseline, after CON, then after INT. Anticipated outcomes: Chronic passive heat stress will decrease chronic inflammation, improve glucose utilization and improve endothelial function. Preliminary studies and future directions: This work utilizes a feasible and practical method of passive heating using electrical heating blankets and water perfused suits that has been well-developed in Dr. Trbovich’s lab.11 This proposal takes next steps to collect pilot data to investigate a potential therapeutic effect of this practical passive heating method to on leading causes of morbidity and mortality post-SCI.