Hypoxia, Ventricular Dysfunction, Right
Conditions
Brief summary
The purpose of this study is to better understand how hypoxia (low oxygen) affects resting and exertional right ventricular function in healthy individuals.
Detailed description
The right ventricle plays a critical role in exercise. As workload increases with exercise, the right ventricle augments contractility and lusitropy (diastolic relaxation) to accommodate increased venous return (preload) and pulmonary arterial pressure (afterload). Using gold-standard pressure-volume analysis, the investigators have shown that impairments in right ventricular function limit functional capacity among individuals with cardiovascular disease, heart failure and pulmonary hypertension. In addition, the investigators have characterized right ventricular function during exercise in the healthy heart using these techniques. Hypoxia increases pulmonary arterial pressure via hypoxic pulmonary vasoconstriction. By increasing right ventricular afterload, hypoxia may compromise exercise capacity. However, data regarding the impact of hypoxia on right ventricular performance are lacking. This is a human physiology study of resting and exertional right ventricular function under control (normoxic) and hypoxic conditions. The investigators will use pressure-volume analysis in conjunction with Swan-Ganz catheterization and echocardiography to assess right ventricular performance in healthy individuals at rest and during exercise in normoxia and hypoxia. The study protocol consists of three visits. * Visit 1: Non-invasive symptom-limited cardiopulmonary exercise test under normoxic conditions (FiO2= 0.21). * Visit 2: Non-invasive symptom-limited cardiopulmonary exercise test under hypoxic conditions (FiO2=0.12). * Visit 3: Invasive resting and exertional hemodynamic assessment under normoxic and hypoxic conditions In Visits 1 and 2, heart rate/rhythm, oxygen saturation, blood pressure, gas exchange parameters (oxygen uptake \[VO2\], carbon dioxide production \[VCO2\], and minute ventilation), and rated perceived exertion will be monitored. Cardiopulmonary exercise testing (CPET) will be performed on an upright cycle ergometer with workload starting at 0 Watts and increasing every 2 minutes until volitional exhaustion with maximum workload at 8-12 minutes. The order of Visits 1 and 2 will be randomized to reduce the potential for bias from a learning/ordering effect. In Visit 3, the same non-invasive measurements will be obtained. Additionally, right heart catheterization with Swan-Ganz catheter and conductance catheter placement will be performed. This will provide gold-standard hemodynamic and pressure-volume loop analysis to measure outcomes of right ventricular contractility, lusitropy (diastolic relaxation), afterload, and ventricular-arterial coupling. First, participants will complete submaximal exercise at FiO2=0.21. Submaximal exercise will include 5 minutes at 50% of baseline maximal oxygen uptake (VO2max achieved during Visit 1). After 20 minutes' rest, hemodynamic measurements will be obtained at rest at FiO2 0.21, 0.17, 0.15 and 0.12 to characterize the impact of progressive hypoxia on resting right ventricular hemodynamics. Participants will then perform submaximal exercise (50% VO2 max from hypoxic baseline at Visit 2) at FiO2 0.12. Thereafter, participants will complete a symptom-limited CPET at FiO2 0.12 with monitoring of invasive hemodynamics.
Interventions
OTHERHypoxia
Individuals will be exposed to varying levels of hypoxia according to the protocol detailed above.
Sponsors
University of Colorado, Denver
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18 - 60 * For women, premenopausal status
Exclusion criteria
* Active cardiovascular or pulmonary disease (e.g. hypertension, coronary artery disease, cardiomyopathy, arrhythmia, valvular abnormalities, diabetes, peripheral vascular disease, tobacco use, chronic obstructive pulmonary disease, asthma, interstitial lung disease, restrictive lung disease, or pulmonary hypertension) * Use of cardiac- or pulmonary-related medications * Prior history of high altitude pulmonary edema or high altitude cerebral edema * Body mass index \< 18.5 or \> 30 * Anemia * Iron deficiency * Iron supplementation (oral or intravenous) in the preceding 60 days * Systemic anticoagulation or aspirin use that cannot be temporarily held for the study * Pregnancy * Non-cardiopulmonary disorders that adversely influence exercise ability (e.g. arthritis or peripheral vascular disease) * Dedicated athletic training (defined here as spending \>9 hours per week in vigorous physical activity \[≥6 mets\]) * Regular high-altitude exercise (defined here as engaging in vigorous physical activity \[≥1 hour at ≥6 mets\] at ≥8,000 ft for \>2 days per week over the preceding 4 weeks) * Residence at ≥8,000 ft for 3 or more consecutive nights in the preceding 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Right ventricular contractility measured by conductance catheter | Up to 1 hour | End-systolic elastance (Ees) in mmHg/mL |
| Right ventricular lusitropy (diastolic function) measured by conductance catheter | Up to 1 hour | Minimum dp/dt in mmHg/sec |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac output derived from right heart catheterization | Up to 1 hour | In L/min, calculated by Fick equation |
| Workload | Up to 1 hour | Workloads attained with submaximal and maximal exercise testing |
| Right ventricular stroke work measured by conductance catheter | Up to 1 hour | Area of pressure-volume loop |
| Plasma acylcarnitine 10:0 measured by peripheral venous metabolomics (ultra-high performance liquid chromatography coupled to mass spectrometry) | Up to 1 hour | Relative ion count |
| Red blood cell acylcarnitine 10:0 measured by peripheral venous metabolomics (ultra-high performance liquid chromatography coupled to mass spectrometry) | Up to 1 hour | Relative ion count |
| Maximal oxygen uptake | Up to 1 hour | VO2max achieved in maximal exercise testing |
| Mean pulmonary artery pressure measured by right heart catheterization | Up to 1 hour | In mmHg |
Countries
United States
Outcome results
None listed