Oxygen supply and oxidative phosphorylation limitation in rat myocardium in situ

Abstract

The 1H-NMR signal of the proximal histidyl-NδH of deoxymyoglobin is detectable in the in situ rat myocardium and can reflect the intracellular Po 2. Under basal normoxic conditions, the cellular Po 2 is sufficient to saturate myoglobin (Mb). No proximal histidyl signal of Mb is detectable. On ligation of the left anterior descending coronary artery, the Mb signal at 78 parts/million (ppm) appears, along with a peak shoulder assigned to the corresponding signal of Hb. During dopamine infusion up to 80 μg · kg−1 · min−1, both the heart rate-pressure product (RPP) and myocardial oxygen consumption (MV˙o 2) increase by about a factor of 2. Coronary flow increases by 84%, and O2extraction (arteriovenous O2 difference) rises by 31%. Despite the increased respiration and work, no deoxymyoglobin signal is detected, implying that the intracellular O2 level still saturates MbO2, well above the Po 2at 50% saturation of Mb. The phosphocreatine (PCr) level decreases, however, during dopamine stimulation, and the ratio of the change in Pi over PCr (ΔPi/PCr) increases by 0.19. Infusion of either pyruvate, as the primary substrate, or dichloroacetate, a pyruvate dehydrogenase activator, abolishes the change in ΔPi/PCr. Intracellular O2 supply does not limit MV˙o 2, and the role of ADP in regulating respiration in rat myocardium in vivo remains an open question.