P-31 MAGNETIC-RESONANCE SPECTROSCOPY OF THE SHERPA HEART - A PHOSPHOCREATINE ADENOSINE-TRIPHOSPHATE SIGNATURE OF METABOLIC DEFENSE AGAINST HYPOBARIC HYPOXIA

Of all humans thus far studied, Sherpas are considered by many high-al titude biomedical scientists as most exquisitely adapted for life unde r continuous hypobaric hypoxia, However, little is known about how the heart is protected in hypoxia, Hypoxia defense mechanisms in the Sher pa heart were explored by in vivo, noninvasive P-31 magnetic resonance spectroscopy, Six Sherpas were examined under two experimental condit ions [normoxic (21% F1O2) and hypoxic (11% F1O2)] and in two adaptatio nal states-the acclimated state (on arrival at low-altitude study site s) and the deacclimating state (4 weeks of ongoing exposure to low alt itude), Four lowland subjects were used for comparison, We found that the concentration ratios of phosphocreatine (PCr)/adenosine triphospha te (ATP) were maintained at steady-state normoxic values (0.96, SEM = 0.22) that were about half those found in normoxic lowlanders (1.76, S EM = 0.03) monitored the same way at the same time, These differences in heart energetic status between Sherpas and lowlanders compared unde r normoxic conditions remained highly significant (P < 0,02) even afte r 4 weeks of deacclimation at low altitudes, In Sherpas under acute hy poxia, the heart rate increased by 20 beats per min from resting value s of about 70 beats per min, and the percent saturation of hemoglobin decreased to about 75%, However, these perturbations did not alter the PCr/ATP concentration ratios, which remained at about 50% of the valu es expected in healthy lowlanders, Because the creatine phosphokinase reaction functions close to equilibrium, these steady-state PCr/ATP ra tios presumably coincided with about 3-fold higher free adenosine diph osphate (ADP) concentrations, Higher ADP concentrations (i.e., lower [ PCr]/[ATP] ratios) were interpreted to correlate with the K-m values f or ADP-requiring kinases of glycolysis and to reflect elevated carbohy drate contributions to heart energy needs, This metabolic organization is postulated as advantageous in hypobaria because the ATP yield per O-2 molecule is 25-60% higher with glucose than with free fatty acids (the usual fuels utilized in the human heart in postfasting conditions ).