Impact of Hypoxia on Resting and Exertional Right Ventricular Performance
Condition: Ventricular Dysfunction, Right; Hypoxia
MeSH terms: Ventricular Dysfunction; Ventricular Dysfunction, Right; Hypoxia
Study type: Observational

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.
    

Intervention name(s): Hypoxia
Intervention type(s): Other
Intervention description(s): Individuals will be exposed to varying levels of hypoxia according to the protocol detailed above.
Observational model: Other
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        10 healthy men and women