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，瘦肌肉质量的减少，自主神经功能障碍，以及相对的身体功能障碍， 不活动（与身体健全的人口相比）有助于心血管疾病的发展 (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，慢性低度炎症，其特征是静息浓度升高， 促炎细胞因子介导了这种关系。4 SCI患者的促炎细胞因子浓度升高， 促炎标志物与健全（AB）个体相比，3，5葡萄糖利用受损， 在受伤后3-6周内发生的血管重塑。6，7在健全（AB）人群中， 运动训练增加瘦体重，提高葡萄糖利用率，重要的是，还减少了慢性 低度炎症，可能通过白细胞介素（IL）-6血浆浓度的急性增加， 虽然运动是一种具有成本效益的干预措施，可以降低 慢性疾病的风险，SCI患者的身体能力下降往往妨碍参与 与AB人相比，在SCI中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）和慢性（4-8次以上的重复治疗） 周）被动加热可以减少AB人的炎症。在SCI患者中，急性（1 ~ 60分钟会话）被动热疗法减少炎症，但仅在短时间内。影响发病率 和死亡率，将需要炎症的长期衰减，因此，慢性（即; 重复会话）在较长时间段内的被动热疗法需要被研究。这是第一项研究 研究慢性被动热疗对SCI患者的影响， 炎症、葡萄糖利用和内皮功能。我们假设六周的被动治疗 热疗法将减少炎症介质、葡萄糖利用和内皮功能。 方法：10名感觉运动完全性（AIS A）SCI患者（C2-T6级）将参加8周的研究 无被动加热（对照= CON），随后进行8周的被动热应激（干预= INT）， 电热毯60分钟2- 3次/周。炎症标志物（TLR 4、Hsp 70、CRP、IL-6、TNF-α、IL-1β、 IL-10）、口服葡萄糖耐量和皮肤血流量变化与局部热高血症（一氧化氮 依赖）将在基线、CON后、INT后进行测量。预期结局：慢性被动 热应激将减少慢性炎症、改善葡萄糖利用和改善内皮功能。 初步研究和未来的方向：这项工作利用了一种可行的和实用的被动方法， 加热使用电热毯和水灌注西装，已在博士开发良好。 Trbovich的实验室。11该提案采取下一步措施收集试点数据，以研究潜在的治疗方法。 这种实用的被动加热方法对SCI后发病率和死亡率的主要原因的影响。