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

被动加热作为一种可行且可耐受的策略，可改善脊髓损伤患者的炎症状况和心脏代谢健康

• 批准号: 10623141
• 负责人: Michelle Trbovich
• 金额: --
• 依托单位: SOUTH TEXAS VETERANS HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10623141
• 关键词: Acclimatization; Acute; Anti-Inflammatory Agents; Antiinflammatory Effect; Autonomic Dysfunction; Biological Markers; Blood Pressure; Blood Vessels; Blood flow; Cardiovascular Diseases; Caring; Cause of Death; Cervical spinal cord injury; Chronic; Chronic Disease; Crossover Design; Cutaneous; Data; Development; Diabetes Mellitus; Endothelium; Equation; Exercise; Exposure to; Flow Cytometry; Functional disorder; Future; Glucose; Goals; HSP72 protein; Health; Health Benefit; Heart Diseases; Heat Stress Disorders; Heating; Home; Hour; Immersion; Impairment; Incidence; Individual; Inflammation; Inflammation Mediators; Inflammatory; Injury; Interleukin-1 beta; Interleukin-10; Interleukin-6; Intervention; Laboratories; Laser-Doppler Flowmetry; Leg; Limb structure; Lower Extremity; Measures; Mediating; Medical; Metabolic Diseases; Metabolism; Methods; Morbidity - disease rate; Muscular Atrophy; Nitric Oxide; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Outcome; Paralysed; Perfusion; Persons; Physical Capacity; Pilot Projects; Plasma; Population; Protocols documentation; Reporting; Research; Rest; Risk; Risk Factors; Risk Reduction; Skin; Skin Temperature; Spinal cord injury; Structure; TLR4 gene; TNF gene; Temperature; Testing; Therapeutic Effect; Therapeutic heat application; Thinness; Time; Translating; Vascular remodeling; Vasodilation; Vasodilator Agents; Water; Work; arm; attenuation; cardiometabolism; cost; cost effective intervention; cytokine; efficacy testing; exercise training; glucose metabolism; improved; inflammatory marker; insulin signaling; lean body mass; monocyte; mortality; muscle form; oral glucose tolerance; physical inactivity; power analysis; programs; reduced muscle mass; response; sedentary lifestyle; shear stress

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.

脊髓损伤后，瘦肉量减少，自主神经功能障碍，以及相对生理 缺乏运动(与健全的人群相比)有助于心血管疾病的发展 心血管疾病(CVD)和2型糖尿病(T2 DM)是发病率和死亡率的主要原因。 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脊髓损伤患者血浆中的 促炎标志物与健全(AB)个体的比较，3，5受损的葡萄糖利用和 血管重构最快发生在损伤后3-6周。6，7在健全(AB)人群中， 运动训练增加了瘦体重，提高了葡萄糖的利用率，更重要的是，还减少了慢性 低级别炎症，可能是通过血浆白细胞介素6和 每次会议后服用抗炎细胞因子。10虽然锻炼是一种成本效益高的干预措施，可以降低 慢性病的风险，脊髓损伤患者的体能下降往往排除了参与 与AB患者相比，运动和运动的抗炎益处在脊髓损伤患者中看不到。的确有 越来越多和新出现的证据表明，急性(仅1次)和慢性(重复4-8次) 周)被动加热可减轻AB患者的炎症反应。在脊髓损伤患者中，急性(1 ~60分钟疗程)被动热疗可减少炎症，但只能持续很短的时间。影响发病率 而死亡率、炎症的长期减轻将是必需的，因此，慢性(即； 重复治疗)，需要研究更长时间内的被动热疗。这是第一次研究 探讨慢性被动热疗对脊髓损伤患者的影响及其对 炎症、葡萄糖利用和内皮功能。我们假设六个星期的被动 热疗会降低炎症介质、葡萄糖利用率和内皮功能。 方法：10名感觉运动完全性(AISA)脊髓损伤(C2-T6级)患者参加为期8周的实验 没有被动加热(对照组=CON)，然后是8周的被动热应激(干预=INT)，使用 电热毯，每周2-3次，每次60分钟。炎症标志物(TLR4、HSP70、C反应蛋白、IL-6、肿瘤坏死因子-α、IL-1β、 白介素10)、口服糖耐量和局部热性高血症皮肤血流量的变化(一氧化氮 从属)将在基线、CON之后、INT之后测量。预期结果：长期被动 热应激可减轻慢性炎症，提高葡萄糖利用率，改善内皮功能。 初步研究和未来方向：本工作利用了一种可行而实用的被动方法 使用电热毯和冲水套装供暖，这在Dr。 Trbovich的实验室11.这项提议采取下一步收集试验数据以调查潜在的治疗方法 这种实用的被动加热方法对脊髓损伤后发病率和死亡率的影响。