The Biology of Chronic Preconditioning: Genomic and Physiologic Mechanisms of Response
Summary
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
Description
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 Design
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science
Conditions
Ischemic Preconditioning
Intervention
Remote ischemic preconditioning (RIPC), Exercise
Location
The Hospital for Sick Children
Toronto
Ontario
Canada
M5G 1X8
Status
Recruiting
Source
The Hospital for Sick Children
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01164618
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Ischemic Postconditioning
The application of repeated, brief periods of vascular occlusion at the onset of REPERFUSION to reduce REPERFUSION INJURY that follows a prolonged ischemic event. The techniques are similar to ISCHEMIC PRECONDITIONING but the time of application is after the ischemic event instead of before.
Ischemic Preconditioning
A technique in which tissue is rendered resistant to the deleterious effects of prolonged ischemia and reperfusion by prior exposure to brief, repeated periods of vascular occlusion. (Am J Physiol 1995 May;268(5 Pt 2):H2063-7, Abstract)
Ischemic Preconditioning, Myocardial
Exposure of myocardial tissue to brief, repeated periods of vascular occlusion in order to render the myocardium resistant to the deleterious effects of ISCHEMIA or REPERFUSION. The period of pre-exposure and the number of times the tissue is exposed to ischemia and reperfusion vary, the average being 3 to 5 minutes.
Optic Neuropathy, Ischemic
Ischemic injury to the OPTIC NERVE which usually affects the OPTIC DISK (optic neuropathy, anterior ischemic) and less frequently the retrobulbar portion of the nerve (optic neuropathy, posterior ischemic). The injury results from occlusion of arterial blood supply which may result from TEMPORAL ARTERITIS; ATHEROSCLEROSIS; COLLAGEN DISEASES; EMBOLISM; DIABETES MELLITUS; and other conditions. The disease primarily occurs in the sixth decade or later and presents with the sudden onset of painless and usually severe monocular visual loss. Anterior ischemic optic neuropathy also features optic disk edema with microhemorrhages. The optic disk appears normal in posterior ischemic optic neuropathy. (Glaser, Neuro-Ophthalmology, 2nd ed, p135)
Reperfusion
Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing REPERFUSION INJURY.
Clinical Trials
The Effect of Remote Ischemic Preconditioning in the Cardiac Surgery
Perioperative myocardial injury is a serious complication of cardiac surgery. This complication increases both mortality and morbidity of cardiac surgery. Remote ischemic preconditioning (...
Clinical and Genomic Responses to Open Heart Surgery
This study will be the first large scale randomized study of remote ischemic preconditioning (RIPC) ever performed and will define the role of this novel therapy as a clinical tool. This s...
In recent several clinical trials, remote preconditioning showed very powerful myocardial protection. However, the myocardial protective effect by remote preconditioning was not evaluated...
Effect of Remote Ischemic Preconditioning on Cardiac Function After Cardiac Surgery
The purpose of this study is to evaluate the effects of Remote Ischemic Preconditioning on cardiac function in patients undergoing cardiac surgery compared to control intervention.
Remote Ischemic Preconditioning in ad Hoc Percutaneous Coronary Interventions
Elective percutaneous coronary intervention (PCI) is associated with troponin release in approximately one third of cases. Myocardial necrosis may result from downstream embolization of at...
PubMed Articles
Background: Myocardial injury is associated with an adverse outcome after off-pump coronary artery bypass graft surgery (OPCAB). The authors conducted a randomized controlled trial to evaluate whether...
Exercise preconditioning and brain ischemic tolerance.
It is well established that physical exercise can exert neuroprotection both in clinical settings and animal experiments. A series of studies have demonstrated that physical exercise may be a promisin...
The purpose of this study was to assess the effect of remote ischemic precondition (RIPC) on the incidence of myocardial and renal injury in patients undergoing cardiovascular interventions as measure...
Ischemic postconditioning is a concept originally defined to contrast with that of ischemic preconditioning. While both preconditioning and postconditioning confer a neuroprotective effect on brain is...
BACKGROUND: The mechanism underlying remote ischemic conditioning (RIC) remains unclear. We investigated whether RIC protects the heart through the activation of the adenosine re...
