Role of Sympathetic Activation in Ischemia Reperfusion Injury

Study Overview
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Brief Summary
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This study is designed to assess the effect of forearm ischemia-reperfusion injury on sympathetic nerve activity. To determine whether reduced sympathetic responsiveness is a contributor to the protective effects of remote ischemic preconditioning. In addition it will assess whether pharmacologic inhibition of the sympathetic nervous system can ameliorate ischemia reperfusion injury induced endothelial dysfunction.

Detailed Description
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This is a randomized single blind study where subjects will be allocated to undergo one of the 4 protocols. Participants will be given placebo or 0.2mg of Moxonidine to take orally 20 minutes prior to the first endothelial function measurement. This medication acts by reducing the activity of nerves believed to be involved in the conditioning process. The placebo pill, designed to have no effect, will be used as a comparison. Comprehensive tests will occur which include Microneurography, Endothelial function ,Blood Sampling, Temporary block of arm blood flow and Remote conditioning

Official Title
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Role of Sympathetic Activation in Ischemia Reperfusion Injury

Conditions
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Central Sympathetic Nervous System Diseases

Intervention / Treatment
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* Drug: Moxonidine 0.2 MG
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy males, not on any medication, free of any history of metabolic, cardiovascular or cerebrovascular disease. Exclusion Criteria: smoker

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: No conditioning + placebo<br>Participants will be given placebo to take orally 20 minutes prior to the first endothelial function measurement without conditioning tests. | Other: placebo<br>* Subjects will be allocated to undergo conditioning or non conditioning assigned in a randomized order. Participants will be given placebo or 0.2mg of Moxonidine to take orally 20 minutes prior to the first endothelial function measurement.<br>|
| Experimental: No conditioning + moxonidine<br>Participants will be given moxonidine to take orally 20 minutes prior to the first endothelial function measurement without conditioning tests. | Drug: Moxonidine 0.2 MG<br>* Subjects will be allocated to undergo conditioning or non conditioning assigned in a randomized order. Participants will be given placebo or 0.2mg of Moxonidine to take orally 20 minutes prior to the first endothelial function measurement.<br>|
| Experimental: Remote pre-conditioning + placebo<br>Participants will be given placebo to take orally 20 minutes prior to the first endothelial function measurement with conditioning tests. | Other: placebo<br>* Subjects will be allocated to undergo conditioning or non conditioning assigned in a randomized order. Participants will be given placebo or 0.2mg of Moxonidine to take orally 20 minutes prior to the first endothelial function measurement.<br>|
| Experimental: Remote pre-conditioning + moxonidine<br>Participants will be given moxonidine to take orally 20 minutes prior to the first endothelial function measurement with conditioning tests. | Drug: Moxonidine 0.2 MG<br>* Subjects will be allocated to undergo conditioning or non conditioning assigned in a randomized order. Participants will be given placebo or 0.2mg of Moxonidine to take orally 20 minutes prior to the first endothelial function measurement.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in muscle sympathetic nerve activity | Muscle sympathetic nerve activity assessed by microneurography | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial Function using the EndoPat2000 device | Endothelial Function testing involves the measurement of pulse amplitude from the tip of each index finger at rest and after a period of occlusion using an arm cuff that is manually inflated to a level above that of the participant's Blood Pressure (BP). | 2 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ischemia, re-perfusion, Remote conditioning