Bünger R, Swindall B, Brodie D, Zdunek D, Stiegler H, Walter G
J Mol Cell Cardiol. 1986 Apr;18(4):423-38. doi: 10.1016/s0022-2828(86)80905-1.
Function and various parameters of myocardial substrate and energy metabolism were measured in preload-controlled isolated working guinea-pig hearts perfused with normoxic (95% O2) and hypoxic (30 to 45% O2) Krebs-Henseleit buffers ([Ca2+] = 1.25 mM). Energy-yielding substrates were glucose, pyruvate, lactate, and fatty acids (acetate, octanoate). Hypoxia typically produced an increase in coronary flow but a fall in cardiac oxygen uptake (MVO2); left ventricular pressure and work parameters as well as myocardial high energy phosphate levels were decreased while the releases of adenosine plus inosine (V (Ado + Ino)) and lactate were increased. Extra pyruvate (1 to 5 mM) as compared to physiologic concentrations of pyruvate (0.2 mM) produced a relative stabilization of left ventricular pressure and work parameters combined with an attenuation of V (Ado + Ino) provided 5 to 10 mM glucose was the cosubstrate. Coinfusion of 2-deoxyglucose, a nondegradable hexose, in presence of excess pyruvate as sole substrate was without effects on residual ventricular pump function. When 1 mM lactate plus 5 mM glucose were the substrates, hypoxic heart function was also depressed, V (Ado + Ino) was relatively increased, and post-hypoxic recovery of pressure parameters was impaired. Similarly, the fatty acid substrates tested seemed to adversely affect cardiac performance during hypoxia. Extra pyruvate in presence of glucose induced a fall in hypoxic myocardial lactate and alpha-glycerophosphate contents while cellular citrate reached millimolar levels. Obviously, utilizable amounts of glucose were required for pyruvate stabilization of the high flow hypoxic heart. The beneficial effects of pyruvate appeared to depend on a functioning glycolysis; other effects seemed to include redox-related changes in energy state and/or purine nucleoside metabolism as well as a possible citrate buffering of intracellular Ca2+ load.
在预负荷控制的豚鼠离体工作心脏中，使用常氧（95% O₂）和低氧（30%至45% O₂）的克雷布斯 - 亨泽莱特缓冲液（[Ca²⁺]=1.25 mM）灌注，测量心肌底物和能量代谢的功能及各种参数。产能量的底物包括葡萄糖、丙酮酸、乳酸和脂肪酸（乙酸盐、辛酸盐）。低氧通常会导致冠状动脉血流量增加，但心脏摄氧量（MVO₂）下降；左心室压力和做功参数以及心肌高能磷酸水平降低，而腺苷加肌苷的释放量（V (Ado + Ino)）和乳酸释放量增加。与生理浓度的丙酮酸（0.2 mM）相比，额外的丙酮酸（1至5 mM）可使左心室压力和做功参数相对稳定，并使V (Ado + Ino)减弱，前提是5至10 mM葡萄糖作为共底物。在过量丙酮酸作为唯一底物存在的情况下，同时输注不可降解的己糖2 - 脱氧葡萄糖对残余心室泵功能没有影响。当1 mM乳酸加5 mM葡萄糖作为底物时，低氧心脏功能也会受到抑制，V (Ado + Ino)相对增加，低氧后压力参数的恢复受损。同样，所测试的脂肪酸底物在低氧期间似乎对心脏功能有不利影响。葡萄糖存在时额外的丙酮酸会导致低氧心肌乳酸和α - 磷酸甘油含量下降，而细胞内柠檬酸达到毫摩尔水平。显然，高流量低氧心脏中丙酮酸的稳定需要可利用量的葡萄糖。丙酮酸的有益作用似乎取决于糖酵解的正常运作；其他作用似乎包括能量状态和/或嘌呤核苷代谢中与氧化还原相关的变化，以及细胞内Ca²⁺负荷的可能的柠檬酸盐缓冲作用。
