The Role of S-nitrosohemoglobin in Regulating Systemic Blood Flow During Hypoxia and Normoxia

Study Overview
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Brief Summary
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Nitric oxide is believed to contribute to regulation of blood flow by its selective binding to circulating hemoglobin (forming S-nitrosohemoglobin, SNO-Hb) and release in a PO2-dependent manner. This study is designed to test that hypothesis by measuring the effect of hypoxia and exercise on forearm blood flow before and after depletion of SNO-Hb using oral N-acetylcysteine.

Detailed Description
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NO has been shown to associate with erythrocytes in the form of SNO-Hb and can deliver vasomotor changes as erythrocytes pass through a physiologic O2 gradient. The aim of this study is to transiently deplete circulating SNO-Hb levels to prove that these levels are directly linked with the normal physiological vasodilation that occurs in response to brief hypoxia that occurs in moderate exercise. This study will be performed on healthy volunteers especially with no predisposing cardiovascular or respiratory conditions that may change their vasomotor response to hypoxia. Systemic blood flow will be approximated using non-invasive forearm venous occlusion plethysmography which will be performed initial to gather baseline data. The participants will then undergo 4 days of 600 mg BID oral N-acetylcysteine (NAC) solution treatment which acts as a bait reactant for NO groups bound to hemoglobin (SNO-Hb) and will then undergo retesting with forearm plethysmography. At the time of both blood flow measurements, arterial blood samples will also be gathered via an arterial catheter inserted on each of two testing days to determine SNO-Hb levels. Statistical analysis will include measuring the blunting of the hypoxia response and SNO-Hb levels using baseline testing as a self-control for each participant. Large scale human placebo-controlled trials with high-dose oral NAC (up to 8000 mg/day) for periods up to 12 months have shown no clinically significant adverse reactions, much less than in the proposed study.

Official Title
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The Role of S-nitrosohemoglobin in Regulating Systemic Blood Flow Under Hypoxic and Normoxic Conditions

Conditions
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Focus is Determination of the Role of SNO-Hb in Forearm Blood Flow Regulation

Intervention / Treatment
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* Drug: Oral N-acetylcysteine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers Exclusion Criteria: Pregnancy smoking pulmonary disease cardiovascular disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-Acetylcysteine (NAC)<br>After initial measurements of SNO-Hb level, forearm blood flow in response to exercise and hypoxia, subjects will take oral NAC 600 mg twice daily. Measurements will then be repeated. | Drug: Oral N-acetylcysteine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forearm blood flow |  | 5 days |