Intracellular energetics and critical PO2 in resting ischemic human skeletal muscle in vivo

Lanza IR, Tevald MA, Befroy DE, Kent-Braun JA. Intracellular energetics and critical PO2 in resting ischemic human skeletal muscle in vivo. Am J Physiol Regul Integr Comp Physiol 299: R1415-R1422, 2010. First published September 1, 2010; doi:10.1152/ajpregu.00225.2010.-During ischemia and some types of muscular contractions, oxygen tension (PO2) declines to the point that mitochondrial ATP synthesis becomes limited by oxygen availability. Although this critical PO2 has been determined in animal tissue in vitro and in situ, there remains controversy concerning potential disparities between values measured in vivo and ex vivo. To address this issue, we used concurrent heteronuclear magnetic resonance spectroscopy (MRS) to determine the critical intracellular PO2 in resting human skeletal muscle in vivo. We interleaved measurements of deoxymyoglobin using H-1-MRS with measures of high-energy phosphates and pH using P-31-MRS, during 15 min of ischemia in the tibialis anterior muscles of 6 young men. ATP production and intramyocellular PO2 were quantified throughout ischemia. Critical PO2, determined as the PO2 corresponding to the point where PCr begins to decline (PCrip) in resting muscle during ischemia, was 0.35 +/- 0.20 Torr, means +/- SD. This in vivo value is consistent with reported values ex vivo and does not support the notion that critical PO2 in resting muscle is higher when measured in vivo. Furthermore, we observed a 4.5-fold range of critical PO2 values among the individuals studied. Regression analyses revealed that time to PCrip was associated with critical PO2 and the rate of myoglobin desaturation (r = 0.83, P = 0.04) but not the rate of ATP consumption during ischemia. The apparent dissociation between ATP demand and myoglobin deoxygenation during ischemia suggests that some degree of uncoupling between intracellular energetics and oxygenation is a potentially important factor that influences critical PO2 in vivo.