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: 10363298
• 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/10363298
• 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; Persons; Physical Capacity; Pilot Projects; Plasma; Population; Protocols documentation; Reporting; Research; Rest; Risk; Risk Factors; 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; 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，自主功能障碍和相对物理的减少 不活跃（与身体健全的人群相比）有助于心血管疾病的发展 （CVD）和2型糖尿病（T2DM）是发病率和死亡率的主要原因。1-3有 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 促炎性细胞因子，调解这种关系。4SCI患者的浓度升高 促炎性标记物与健美（AB）个体相比，葡萄糖利用率受损3,5 受伤后3-6周发生的血管重塑。 锻炼训练可以增加体重，改善葡萄糖利用率，并且重要的是减少了慢性 低度炎症，有可能通过血浆（IL）-6的血浆浓度急性增加 每次会议之后的抗炎细胞因子。10运动是一种具有成本效益的干预措施，以降低 患有慢性疾病的风险，SCI患者的身体能力降低通常会规定参与 与AB人相比，SCI中没有看到运动和抗炎的益处。有 增长和新兴的证据表明急性（仅1次）和慢性（4-8岁以上的重复会议） 几周）被动加热可以减少AB患者的炎症。在患有SCI的人中，急性（一个 〜60分钟疗程）被动热疗法会降低感染，但仅在短时间内。影响发病率 和死亡率，长期炎症的长期衰减将需要，因此，慢性的影响（即； 重复会议）需要研究较长时间内被动热疗法。这是第一个研究 调查慢性被动热疗法对SCI患者的影响及其对 炎症，葡萄糖利用和内皮功能。我们假设被动六个星期 热疗法将降低炎症介质，葡萄糖利用率和内皮功能。 方法：十个有感觉运动完整的人（AIS A）SCI（C2-T6级）将在8周内参加 没有被动加热（控制= con），然后使用8周的被动热应力（干预= INT） 每周60分钟2-3倍的电加热毯。炎症标记（TLR4，HSP70，CRP，IL-6，TNF-α，IL-1β， IL-10），口服葡萄糖耐受性和皮肤血流随局部热症（一氧化氮）而变化 依赖性）将在基线，con之后，然后在int之后进行测量。抗后果：慢性被动 热应力将减少慢性注射，改善葡萄糖利用并改善内皮功能。 初步研究和未来方向：这项工作利用了一种可行且实用的被动方法 使用电气加热毯和水灌注西服的加热，这些西服已在Dr. Trbovich的实验室。11该提案采取下一步收集试点数据以调查潜在的疗法 这种实际被动加热方法对SCI后发病和死亡率的主要原因的影响。