Mitochondrial function in normal and hypoxic states of the myocardium.
The relationships among isometric tension development, the oxidation-reduction states of pyridine nucleotides and cytochrome c, and the oxygenation state of myoglobin have been assessed using the arterially perfused rabbit interventricular septum under different conditions of contraction rate, perfusate [Ca2+] and pH, catecholamine stress, and hypoxia. Hypoxia was produced either by decreasing oxygen availability with maintained flow (high-flow hypoxia) or by decreasing the flow rate (ischemia). Under normoxic conditions, increased work caused a fall of the cytosolic adenine nucleotide phosphorylation potential, delta G(ATP)c, an oxidation of the pyridine nucleotides, and a reduction of cytochrome c; the opposite occurred with decreased work. Thus, the redox potential span from NADH to cytochrome c, delta Eh, varied with the energy demand such that delta Eh and delta G(ATP)c changed in the same direction. Under hypoxic conditions, all respiratory components became more reduced, and myoglobin was partially deoxygenated. The percentage change of developed tension under hypoxic conditions was approximately proportional to the percentage change of oxidized cytochrome c. When high-flow hypoxia and ischemia were compared at the same rates of oxygen delivery, the developed tension at any level of cytochrome c reduction was always lower with ischemia than with high-flow hypoxia. This difference was attributed to the low intracellular pH of ischemic tissue. Myoglobin deoxygenation was linearly related to cytochrome c reduction under all conditions of hypoxia, indicating steep oxygen gradients. The results support the concept of heterogeneous oxygenation of the tissue with mixed populations of aerobic and anaerobic mitochondria in the hypoxic state. In the full aerobic state, the control of mitochondrial respiration in situ appears similar to that of isolated mitochondria.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D009200:Myocardial Contraction; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D011817:Rabbits
D003574:Cytochrome c Group; D009243:NAD; D003576:Electron Transport Complex IV; D002118:Calcium