Hyperoxia and Microvascular Dysfunction

NCT ID: NCT04321434

Last Updated: 2020-03-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-01
• Study Completion Date: 2018-10-01

Brief Summary

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:

1. Endothelial dysfunction observed at the level of microvascular cardiac arteries is readily present at the level of subcutaneous microcirculation in a given CAD patient.

2. 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.

3. 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.

4. 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.

Conditions

Coronary Microvascular Disease; Microvascular Disease; Ischemic Heart Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Hyperoxia

• 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

Group Type: EXPERIMENTAL

Hyperoxia

Intervention Type: OTHER

laser Doppler

Intervention Type: DEVICE

laser Doppler

Normoxia

• 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

Group Type: PLACEBO_COMPARATOR

Normoxia

Intervention Type: OTHER

laser Doppler

Intervention Type: DEVICE

laser Doppler

Interventions

Hyperoxia

Intervention Type: OTHER

Normoxia

Intervention Type: OTHER

laser Doppler

laser Doppler

Intervention Type: DEVICE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Université Libre de Bruxelles

OTHER

Sponsor Role: lead

Responsible Party

Martin Chaumont

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jean-Paul Van Vooren, MD, PhD

Role: STUDY_DIRECTOR

Hospital Erasme

Locations

Erasme Hospital

Brussels, Brabant, Belgium

Countries

Belgium

Other Identifiers

P2016/043/B406201627021

Identifier Type: -

Identifier Source: org_study_id