Oxygen supply and oxidative phosphorylation limitation in rat myocardium in situ.
The 1H-NMR signal of the proximal histidyl-N(delta)H of deoxymyoglobin is detectable in the in situ rat myocardium and can reflect the intracellular PO2. Under basal normoxic conditions, the cellular PO2 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 microg. kg(-1) x min(-1), both the heart rate-pressure product (RPP) and myocardial oxygen consumption (MVO2) increase by about a factor of 2. Coronary flow increases by 84%, and O2 extraction (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 PO2 at 50% saturation of Mb. The phosphocreatine (PCr) level decreases, however, during dopamine stimulation, and the ratio of the change in P(i) over PCr (DeltaP(i)/PCr) increases by 0.19. Infusion of either pyruvate, as the primary substrate, or dichloroacetate, a pyruvate dehydrogenase activator, abolishes the change in DeltaP(i)/PCr. Intracellular O2 supply does not limit MVO2, and the role of ADP in regulating respiration in rat myocardium in vivo remains an open question.
Kreutzer
U
U
Department of Biological Chemistry, University of California, Davis, California 95616-8635, USA.
Mekhamer
Y
Y
Chung
Y
Y
Jue
T
T
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose; D002244:Carbon / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D019344:Lactic Acid / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D010313:Partial Pressure; D010725:Phosphocreatine / Q000097:blood; D010759:Phosphorus Isotopes; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D002316:Cardiotonic Agents; D009211:Myoglobin; D010759:Phosphorus Isotopes; D010725:Phosphocreatine; D019344:Lactic Acid; D000244:Adenosine Diphosphate; D002244:Carbon; D000255:Adenosine Triphosphate; D010100:Oxygen; D004298:Dopamine