Normobaric hypoxia impairs human cardiac energetics

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)O(2)) was kept between 50 and 60 mmHg, and peripheral oxygen saturation (SaO(2)) 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 (31)P magnetic resonance spectroscopy. During hypoxia, PETO(2) and SaO(2) 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.-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. Normobaric hypoxia impairs human cardiac energetics. FASEB J. 25, 3130-3135 (2011). www.fasebj.org