Cardiac response to hypobaric hypoxia: persistent changes in cardiac mass, function, and energy metabolism after a trek to Mt. Everest Base Camp

Abstract

We postulated that changes in cardiac high-energy phosphate metabolism may underlie the myocardial dysfunction caused by hypobaric hypoxia. Healthy volunteers (n=14) were studied immediately before, and within 4 d of return from, a 17-d trek to Mt. Everest Base Camp (5300 m). (31)P magnetic resonance (MR) spectroscopy was used to measure cardiac phosphocreatine (PCr)/ATP, and MR imaging and echocardiography were used to assess cardiac volumes, mass, and function. Immediately after returning from Mt. Everest, total body weight had fallen by 3% (P<0.05), but left ventricular mass, adjusted for changes in body surface area, had disproportionately decreased by 11% (P<0.05). Alterations in diastolic function were also observed, with a reduction in peak left ventricular filling rates and mitral inflow E/A, by 17% (P<0.05) and 24% (P<0.01), respectively, with no change in hydration status. Compared with pretrek, cardiac PCr/ATP ratio had decreased by 18% (P<0.01). Whether the abnormalities were even greater at altitude is unknown, but all had returned to pretrek levels after 6 mo. The alterations in cardiac morphology, function, and energetics are similar to findings in patients with chronic hypoxia. Thus, a decrease in cardiac PCr/ATP may be a universal response to periods of sustained low oxygen availability, underlying hypoxia-induced cardiac dysfunction in healthy human heart and in patients with cardiopulmonary diseases.

Pathophysiology and Treatment of High-Altitude Pulmonary Vascular Disease

“…The roles of activation of the sympathetic nervous system, hypovolemia (from hyperventilation and increased diuresis), hypocapnia (from hyperventilation), and myocardial contractility in this response are difficult to discern. 47 On the whole, myocardial contractility is preserved, although reversible reductions in cardiac mass and myocardial phosphocreatine/ ATP have been documented in healthy volunteers after a 17-day trek to 5300 m. 48 Right heart failure is a risk in some previously healthy individuals, precipitated by more extreme pulmonary …”

Tissue-specific changes in fatty acid oxidation in hypoxic heart and skeletal muscle

“…Conversely, PPAR␣ expression is low in hypoxic skeletal muscle, promoting an increased use of carbohydrates to meet energetic demands. The different metabolic responses of these two tissues may explain why human skeletal muscle is apparently able to maintain resting ATP levels following hypoxic exposure, while the heart is energetically impaired (9,17).…”

“…fatty acids; mitochondrial respiration; hypoxia; metabolism; heart HYPOBARIC HYPOXIA elicits a myriad of physiological responses that aim to increase oxygen availability at the tissues or decrease tissue oxygen demand (42). Central to this response is an acute increase in cardiac output, which in the face of atmospheric hypoxia can lead to an inability to match oxygen demand at the heart tissue itself (17). In a study of humans returning from exposure to hypobaric hypoxia at high altitude, resting energy levels were maintained in the subjects' skeletal muscle (9), whereas their hearts showed impaired energetics as indicated by decreased PCr/ATP (17).…”

“…Central to this response is an acute increase in cardiac output, which in the face of atmospheric hypoxia can lead to an inability to match oxygen demand at the heart tissue itself (17). In a study of humans returning from exposure to hypobaric hypoxia at high altitude, resting energy levels were maintained in the subjects' skeletal muscle (9), whereas their hearts showed impaired energetics as indicated by decreased PCr/ATP (17). The cellular mechanisms underlying the different responses of these two tissues are unknown; however, the process of metabolic remodelling may differ under hypoxic conditions, and it has been suggested that altered substrate selection and mitochondrial respiration may be key factors in this regard (23,38,50).…”

“…Given the requirement of the heart for oxygen to drive oxidative phosphorylation, it is highly sensitive to changes in oxygen pressure, and this has a significant effect on substrate use. Hence, the oxygen-deprived heart exhibits decreased mitochondrial respiration and ATP production (10,17). It has been suggested that this energy deprivation may result from an inhibition of fatty acid oxidation (25), coupled with an incomplete compensation by glucose oxidation (8,37,46,49).…”