Cardiovascular Safety Of Severe And Sustained Hypoxia Exposure In Physically Fit Patients Following Myocardial Infarction

In mice, hypoxia exposure corresponding to 8000 m altitude over several weeks induced myocardial proliferation and improved left ventricular ejection fraction following myocardial infarction. To enable translation of these findings from mice to patients with myocardial infarction, we determined whether exposure to severe sustained hypoxia is limited by right ventricular failure secondary to hypoxia-induced pulmonary hypertension. We enrolled three men who suffered myocardial infarctions 49-126 months prior to the study (left ventricular ejection fraction 47±7 %) but were otherwise healthy and one male, healthy control person. We induced hypoxia by adding nitrogen to ambient air until alveolar oxygen partial pressure decreased to 35 mmHg. Normobaric hypoxia was then maintained for 14 consecutive days (FiO2=0.095) corresponding to 6062- 6224 m altitude. We added 1% oxygen over night to ameliorate sleep and prevent acute mountain sickness. We conducted echocardiography at baseline, during hypoxia in hypoxic conditions and 3 days after reconditioning. Measurements included right ventricular to atrial pressure gradient as surrogate for pulmonary artery systolic pressure (PAPsys), tricuspid annulus systolic excursion (TAPSE) and right ventricular (RV) free wall strain. Hypoxia induced pulmonary hypertension, that rapidly abated in recovery (baseline: 35±3 mmHg, hypoxia: 47±9, recovery: 28±1, p=0.0292). TAPSE was not reduced by hypoxic exposure (baseline: 28±3 mmHg, hypoxia: 26±1 recovery: 29±2, p=0.0693) and right ventricular free wall strain was maintained (baseline: -22.4±3.9 mmHg, hypoxia: -24±5.4 recovery: -22.7±1.5, p=0.8493). The healthy control person showed similar responses. No signs or symptoms of right heart failure occurred throughout the study. In highly selected patients with myocardial infarction, substantial normobaric hypoxia induced pulmonary hypertension, however, right ventricular function was well preserved. These observations pave the way for translational studies on hypoxia-induced cardiovascular regeneration and may have implications for patients traveling to high altitude.