The Effects of Preconditioning on Intramuscular High-Energy Phosphate Levels During Ischemia

Study Overview
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Brief Summary
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Ischemia reperfusion injury may be reduced by ischemic preconditioning. This projects aims to show the effects of short and long time ischemic preconditioning (both sequences 3 x 5 minutes) during and after an ischemic period of 20 minutes in healthy subjects by functional MRI. Ischemia is produces by cuff inflation to a suprasystolic pressure on one tight. Signal is acquired from calf muscles. A cross-over design of 4 to 8 study periods is used, 4 different study days with 2 different MR measurement methods (BOLD imaging and high energy phosphates) are planned.

Official Title
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The Effects of Preconditioning on Intramuscular High-Energy Phosphate Levels During Ischemia

Conditions
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Ischemia

Intervention / Treatment
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* Procedure: preconditioning
* Procedure: no preconditioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men aged between 18 and 45 years Nonsmoker for more than 3 months Body mass index between 18 and 25 kg/m2 Normal findings in medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant Exclusion Criteria: Regular use of medication, abuse of alcoholic beverages, participation in a clinical trial in the 3 weeks preceding the study Evidence of hypertension, pathologic hyperglycemia, hyperlipidemia Treatment in the previous 3 weeks with any drug including over-the-counter drugs Symptoms of a clinically relevant illness in the 2 weeks before the first study day Blood donation during the previous 3 weeks Any metallic, electric, electronic or magnetic device or object not removable Claustrophobia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>baseline MR signal prior to, during and 30 minutes after an ischemic period of 20 minutes | Procedure: no preconditioning<br>* no preconditioning<br>|
| Other: 2<br>baseline MR signal prior to, during and 30 minutes after an ischemic period of 20 minutes with additional 5 minutes of cuff stenosis directly after cuff release | Procedure: no preconditioning<br>* no preconditioning<br>|
| Other: 3<br>short time preconditioning, other details according arm 2 | Procedure: preconditioning<br>* 3 times of five minutes ischemia, produced by cuff inflation to a suprasystolic pressure positioned on the thigh<br>|
| Other: 4<br>long time preconditioning, other details according arm 2 | Procedure: preconditioning<br>* 3 times of five minutes ischemia, produced by cuff inflation to a suprasystolic pressure positioned on the thigh<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cellular high energy phosphate levels and venous pH concentration for 31P MRS |  | during and 30 min after ischemia | 
| Main outcome variables: Change in cellular oxygen saturation for BOLD MRI |  | during and 30 minutes after ischemia | 
| Serum markers of myocellular injury (myoglobin, creatine-kinase) |  | prior to, directly and 24 hours after ischemia | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ischemic Preconditioning, functional MRI, BOLD, Reperfusion