Hyperoxia and Microvascular Dysfunction

Study Overview
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Brief Summary
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Coronary artery disease (CAD) pathophysiology involves endothelium-dependent (e.g. nitric oxide, acetylcholine) and -independent (e.g. adenosine) vascular dilation impairment, which have been demonstrated at the level of small coronary arteries, medium sized peripheral arteries and subcutaneous microcirculation. Oxygen supplementation, which is frequently overused in clinical settings, seems harmful in acute coronary syndromes and increases microvascular resistance in myocardial and subcutaneous microcirculation through alteration of endothelium-dependent and -independent dilation by an oxidative mechanism. Whether endothelial dysfunction, that is well documented at the level of cardiac microcirculation in CAD patients, is also present at the level of subcutaneous microcirculation is unknown. Also, unknown is whether an acute oxidative stress can be used to probe myocardial microcirculatory dysfunction at the level of subcutaneous microcirculation, which is an easily accessible vascular bed for an in vivo assessment of endothelial-dependent and-independent function. Alterations in cutaneous vascular signalling are evident early in the disease processes. Thus, studying subcutaneous circulation in patients with cardiovascular risk factors could provide vascular information early in CAD processes. This study will test the following 4 hypotheses: Endothelial dysfunction observed at the level of microvascular cardiac arteries is readily present at the level of subcutaneous microcirculation in a given CAD patient. An acute oxidative stress such as hyperoxia can be used to test myocardial microcirculatory dysfunction at the level of the more easily accessible subcutaneous microcirculation. Subcutaneous microcirculation of CAD patients has a lesser vasodilatory response to acetylcholine or sodium nipride than matched healthy subjects. In addition, CAD patients are more prone to dermal vasoconstriction in response to oxygen compared to healthy subjects. Taken that oxygen is still too often given in excess in most clinical settings, the aim of this study is to rule out possible pitfalls in coronary pressure and resistance determinations in CAD patients receiving unnecessary oxygen supplementation.

Official Title
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Cardiac and Subcutaneous Microvascular Dysfunction in Patients With Ischemic Heart Disease: Effects of an Acute Oxidative Stress

Conditions
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Coronary Microvascular Disease, Microvascular Disease, Ischemic Heart Disease

Intervention / Treatment
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* Other: Hyperoxia
* Other: Normoxia
* Device: laser Doppler


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Coronary angiography done in the context of suspicion of coronary artery disease (CAD) Exclusion Criteria: Respiratory failure requiring intubation or supplementary oxygen Severe chronic obstructive pulmonary disease Significant arrhythmia precluding waveform analysis (e.g., excessive premature ventricular contractions or atrial fibrillation) Severe valvular heart disease, Suspected elevated central venous pressure (CVP) Heart failure as defined by New York Heart Association class III or IV Previous coronary revascularization or heart transplantation Severe hypertension (systolic pressure >200 mmHg and diastolic pressure >120 mmHg at rest) Contraindications to adenosine infusion Contraindication to acetylcholine (Ach) infusion Severe bronchial asthma.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyperoxia<br>assessment of forearm skin microcirculatory blood flow by laser Doppler perfusion imager at baseline and during hyperemic tests assessment of coronary microcirculatory blood flow at baseline and during hyperemic tests | Other: Hyperoxia<br> <br> Device: laser Doppler<br>* laser Doppler<br>|
| Placebo Comparator: Normoxia<br>assessment of forearm skin microcirculatory blood flow by laser Doppler perfusion imager at baseline and during hyperemic tests assessment of coronary microcirculatory blood flow at baseline and during hyperemic tests | Other: Normoxia<br> <br> Device: laser Doppler<br>* laser Doppler<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the acetylcholine-induced skin blood flow after hyperoxia | Measurement of skin blood flow before, during and after hyperoxia, expressed in perfusion units (arbitrary units). | 1 hour | 
| Change from baseline in the sodium nitroprusside-induced skin blood flow after hyperoxia | Measurement of skin blood flow before, during and after hyperoxia, expressed in perfusion units (arbitrary units). | 1 hour | 
| Change from baseline in the heat-induced skin blood flow after hyperoxia | Measurement of skin blood flow before, during and after hyperoxia, expressed in perfusion units (arbitrary units). | 1 hour | 
| Change from Baseline in the index of microcirculatory resistance Under adenosine after hyperoxia | Measurement of coronary microcirculatory resistance (index of microcirculatory resistance) Under adenosine before and after hyperoxia, expressed in arbitrary units | 10 minutes | 
| Change from Baseline in the index of microcirculatory resistance at rest after hyperoxia | Measurement of coronary microcirculatory resistance (index of microcirculatory resistance) at rest before and after hyperoxia, expressed in arbitrary units | 10 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiac microvascular dysfunction, subcutaneous microvascular dysfunction, ischemic heart disease, oxydative stress