The Biology of Chronic Preconditioning: Genomic and Physiologic Mechanisms of Response
试验速览
- 阶段
- 2 期
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Ischemia-reperfusion injury tolerance
研究概览
简要总结
The purpose of this study is to assess the effects of repeated RIPC and exercise, on exercise performance, skeletal muscle responses and circulating cellular and humoral biology in humans
详细描述
Remote ischemic preconditioning (RIPC) results in a powerful and widespread protective effect against subsequent prolonged ischemia-reperfusion (IR) injury of distant organs and systemic inflammatory responses, both of which are key elements in the evolution of local and multiorgan effects of many clinical IR syndromes. The signal transduction within the target organ to generate ischemia tolerance, and the effects of RIPC on systemic anti-inflammatory pathways, however, remain to be elucidated fully. Particularly, data regarding the mechanisms of 'second window' protection (a resurgence of protection 24-72 hrs after the initial RIPC stimulus) is scant; even less is known of the effects of repeated RIPC, and a potential 'third window' of protection. Our preliminary data and several recent publications have shown that the biology of RIPC and exercise show considerable overlap. This research has raised the possibility of a reciprocal effect between RIPC and exercise, with chronic exercise being a model of the potential effects of 'chronic preconditioning'. This is relevant, as repeated RIPC might be a strategy to improve exercise function in those with limited exercise tolerance e.g. heart failure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age ≥ 18 years,
- •Informed consent
排除标准
- •Contraindication to exercise,
- •Vigorous aerobic/anaerobic exercise in duration of ≥15 minutes during the 21 days prior to commencement of the study, or either of the RIPC or exercise protocol arms,
- •Overt viral or bacterial infection in the 10 days prior to commencement of the study, or during either of the RIPC or exercise protocol arms,
- •Alcohol and/or caffeine consumption in the 10 days prior to, or at any time during the study period
研究组 & 干预措施
Group 1
The subjects in this arm will begin on the daily remote ischemic preconditioning (RIPC) protocol for 10 days. After a 21 day washout period they will then crossover to 10 days of daily exercise.
干预措施: Remote ischemic preconditioning (RIPC) (Procedure)
Group 1
The subjects in this arm will begin on the daily remote ischemic preconditioning (RIPC) protocol for 10 days. After a 21 day washout period they will then crossover to 10 days of daily exercise.
干预措施: Exercise (Other)
Group 2
The subjects in this arm will begin on the exercise protocol for 10 days. After a 21 day washout period they will then crossover to 10 days of daily remote ischemic preconditioning (RIPC).
干预措施: Remote ischemic preconditioning (RIPC) (Procedure)
Group 2
The subjects in this arm will begin on the exercise protocol for 10 days. After a 21 day washout period they will then crossover to 10 days of daily remote ischemic preconditioning (RIPC).
干预措施: Exercise (Other)
结局指标
主要结局
Ischemia-reperfusion injury tolerance
时间窗: Day 10 of the RIPC intervention
This will be done to assess whether chronic preconditioning in humans generates a circulating effector(s) responsible for the generation of cardioprotection in our mouse model of ischemia-reperfusion injury. This measure will be compared over time within groups and between groups.
次要结局
- Change in skeletal muscle metabolic parameters metabolism as measured by 31P-MRS and BOLD fMRI over time within groups and between groups(Days 1, 2 and 10 days of each intervention (RIPC and Excercise))
- Neutrophil Function - adhesion, phagocytotic index, and superoxide production over time within groups and between groups(Days 1, 2 and 10 of each intervention (RIPC and Excercise))
- Exercise Capacity (VO2max) over time within groups and between groups(Day 10 of each intervention (RIPC and Exercise))
- Neutrophil Gene Expression over time within groups and between groups(Days 1, 2 and 10 of each intervention (RIPC and Excercise))
- Ischemia-reperfusion injury tolerance(Days 1, 2 and 10 of each intervention (RIPC and Excercise))
研究者
Andrew Redington
Head, Heart Centre-Cardiology Division
The Hospital for Sick Children