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
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
12
RIPC will be induced using a standard blood pressure cuff and hand anaeroid sphygmomanometer, on the right arm. The subject will be seated, the blood pressure cuff placed on the arm and inflated to a pressure of 200mmHg for 5 minutes (ischemia). The cuff will then be deflated for 5 minutes (reperfusion) completing one cycle of ischemia reperfusion. A total of 4 inflation and deflation cycles will be applied. This protocol of RIPC will be applied daily, for 10 consecutive days.
Subjects will then undergo exercise daily, for 10 consecutive days. A chronic high-intensity interval exercise training protocol standardized to subjects' aerobic power (VO¬2max) will be used. Each exercise session will consist of a 5 min warm-up period followed by 4 sets of 2 min high intensity intervals interspersed with 3 min recovery periods.
The Hospital for Sick Children
Toronto, Ontario, Canada
Ischemia-reperfusion injury tolerance
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.
Time frame: Day 1 of the Excercise intervention
Ischemia-reperfusion injury tolerance
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.
Time frame: Day 1 of the RIPC intervention
Ischemia-reperfusion injury tolerance
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.
Time frame: Day 2 of the Excercise intervention
Ischemia-reperfusion injury tolerance
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.
Time frame: Day 2 of the RIPC intervention
Ischemia-reperfusion injury tolerance
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.
Time frame: Day 10 of the Excercise intervention
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Ischemia-reperfusion injury tolerance
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.
Time frame: Day 10 of the RIPC intervention
Change in skeletal muscle metabolic parameters metabolism as measured by 31P-MRS and BOLD fMRI over time within groups and between groups
Time frame: 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
Time frame: Days 1, 2 and 10 of each intervention (RIPC and Excercise)
Neutrophil Gene Expression over time within groups and between groups
Time frame: Days 1, 2 and 10 of each intervention (RIPC and Excercise)
Ischemia-reperfusion injury tolerance
We will 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.
Time frame: Days 1, 2 and 10 of each intervention (RIPC and Excercise)
Exercise Capacity (VO2max) over time within groups and between groups
Time frame: Day 10 of each intervention (RIPC and Exercise)