Hyperoxia and Microvascular Dysfunction

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

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.

Study Overview

• Status: Terminated
• Conditions: Ischemic Heart Disease; Coronary Microvascular Disease; Microvascular Disease
• Intervention / Treatment: Other: Hyperoxia; Device: laser Doppler; Other: Normoxia

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brabant
    • Brussels, Brabant, Belgium, 1070
      • Erasme Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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	Other: Hyperoxia; Device: laser Doppler; laser Doppler
PLACEBO_COMPARATOR: 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	Device: laser Doppler; laser Doppler; Other: Normoxia

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Université Libre de Bruxelles
• Investigators: Study Director: Jean-Paul Van Vooren, MD, PhD, Hospital Erasme

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (ACTUAL): April 1, 2018
• Study Completion (ACTUAL): October 1, 2018

Study Registration Dates

• First Submitted: January 16, 2017
• First Submitted That Met QC Criteria: March 24, 2020
• First Posted (ACTUAL): March 25, 2020

Study Record Updates

• Last Update Posted (ACTUAL): March 25, 2020
• Last Update Submitted That Met QC Criteria: March 24, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: ischemic heart disease; oxydative stress; cardiac microvascular dysfunction; subcutaneous microvascular dysfunction
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Angina Pectoris; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Ischemia; Microvascular Angina
• Other Study ID Numbers: P2016/043/B406201627021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No