Trial of the Effects of Remote Preconditioning on the Tissue Metabolism During Exercise and Ischemia
Recruitment status was: Active, not recruiting
|Ischemia||Procedure: Real preconditioning Procedure: Sham preconditioning||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind (Participant)
|Official Title:||Single Blind Randomized Controlled Crossover Trial of the Effects of Remote Preconditioning on the Tissue Metabolism During Exercise and Ischemia|
- Improvement in mitochondrial function following the preconditioning as evidenced by a faster rate of recovery of phosphocreatinine after exercise. [ Time Frame: 2 hours ]
- Improvement of endothelial and microvascular dysfunction induced by 20 minutes of forearm ischemia. [ Time Frame: 1 hour ]
|Study Start Date:||November 2008|
|Estimated Study Completion Date:||June 2014|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Procedure: Real preconditioning
Preconditioning will consist of four 5 minutes cycles of upper limb ischemia interspaced with 5 minutes of reperfusion, using a blood-pressure cuff inflated to a pressure 15 mmHg greater than systolic arterial pressure.
Procedure: Sham preconditioning
Preconditioning will consist of four 5 minutes cycles of upper limb ischemia interspaced with 5 minutes of reperfusion, using a blood-pressure cuff inflated to a pressure 10mmHg with the same cycling protocol as the real preconditioning.
Ischemic preconditioning is a mechanism that protects tissue against ischemia-reperfusion injury. The protective effect of preconditioning is induced by short periods (1-5 minutes) of non-lethal ischemia to the target tissue, which becomes resistant to a prolonged, otherwise lethal, period of ischemia. Despite its proven potency in experimental models, ischemic preconditioning has not reached widespread clinical application because of the difficulties in applying the stimulus to the target organ (eg Heart, Brain), and even brief ischemia to the target organ can cause dysfunction.
Remote ischemic preconditioning (RIPC) is a more clinically relevant stimulus. It has been shown that preconditioning of one coronary territory induces ischemia protection in other parts of the heart. Subsequently, other studies have shown, in rodent models, that preconditioning of one organ (eg kidney) could induce protection in other organs (eg heart). We recently have confirmed, in a series of animal and human preclinical studies, that this concept can be widened; ultimately showing that four 5-minute episodes of ischemia to the skeletal limb muscles (induced by inflating a standard blood pressure cuff to a level higher than the blood pressure) protects the heart and lungs against ischemia-reperfusion injury in children undergoing cardiac surgery using cardiopulmonary bypass.
The current research is designed to investigate with MRI spectroscopy techonology, the potential physiological mechanisms involved in the protective effects of preconditioning, and the effects of ischemia and exercise.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00791206
|Principal Investigator:||Andrew Redington, MD||The Hospital for Sick Children|