Normobaric hypoxia impairs human cardiac energetics.
Holloway C., Cochlin L., Codreanu I., Bloch E., Fatemian M., Szmigielski C., Atherton H., Heather L., Francis J., Neubauer S., Robbins P., Montgomery H., Clarke K.
Hypoxia causes left ventricular dysfunction in the human heart, but the biochemical mechanism is poorly understood. Here, we tested whether short-term normobaric hypoxia leads to changes in cardiac energetics and early cardiac dysfunction. Healthy male volunteers (n=12, age 24 ± 2 yr) were exposed to normobaric hypoxia in a purpose-built hypoxic chamber. The partial pressure of oxygen during end-tidal expiration (P(ET)o₂) was kept between 50 and 60 mmHg, and peripheral oxygen saturation (Sao₂) was kept above 80%. Cardiac morphology and function were assessed using magnetic resonance imaging and echocardiography, both before and after 20 h of hypoxic exposure, and high-energy phosphate metabolism [measured as the phosphocreatine (PCr)/ATP ratio] was measured using ³¹P magnetic resonance spectroscopy. During hypoxia, P(ET)o₂ and Sao₂ averaged 55 ± 1 mmHg and 83.6 ± 0.4%, respectively. Hypoxia caused a 15% reduction in cardiac PCr/ATP (from 2.0 ± 0.1 to 1.7 ± 0.1, P<0.01) and reduced diastolic function (measured as E/E', rising from 6.1 ± 0.4 to 7.5 ± 0.7, P<0.01). Normobaric hypoxia causes a rapid decrease in high-energy phosphate metabolism in the human cardiac left ventricle, which may lead to a decline in diastolic function. These findings are important in understanding the response of normal individuals to environmental hypoxia, and to situations in which disease reduces cardiac oxygen delivery.