Pyruvate attenuation of hypoxia damage in isolated working guinea-pig heart.

摘要: Function and various parameters of myocardial substrate energy metabolism were measured in preload-controlled isolated working guinea-pig hearts perfused with normoxic (95% O2) hypoxic (30 to 45% Krebs-Henseleit buffers ([Ca2+] = 1.25 mM). Energy-yielding substrates glucose, pyruvate, lactate, fatty acids (acetate, octanoate). Hypoxia typically produced an increase coronary flow but a fall cardiac oxygen uptake (MVO2); left ventricular pressure work as well high phosphate levels decreased while the releases adenosine plus inosine (V (Ado + Ino)) lactate increased. Extra pyruvate (1 5 mM) compared physiologic concentrations (0.2 relative stabilization combined attenuation V Ino) provided 10 mM glucose was cosubstrate. Coinfusion 2-deoxyglucose, nondegradable hexose, presence excess sole without effects on residual pump function. When 1 substrates, heart function also depressed, relatively increased, post-hypoxic recovery impaired. Similarly, acid tested seemed adversely affect performance during hypoxia. induced alpha-glycerophosphate contents cellular citrate reached millimolar levels. Obviously, utilizable amounts required for heart. The beneficial appeared depend functioning glycolysis; other include redox-related changes state and/or purine nucleoside possible buffering intracellular Ca2+ load.