van Bilsen M, van der Vusse G J, Snoeckx L H, Arts T, Coumans W A, Willemsen P H, Reneman R S
Department of Physiology, University of Limburg, Maastricht, The Netherlands.
Pflugers Arch. 1988 Dec;413(2):167-73. doi: 10.1007/BF00582527.
In the present study the hemodynamic and metabolic effects of pyruvate (5 mM), added as cosubstrate to glucose (11 mM) perfused, transiently ischemic, isolated working rat hearts, were evaluated. During 2 h of normoxic perfusion pyruvate improved functional stability, prevented depletion of glycogen and triacylglycerol stores, and increased non-esterified fatty acid (NEFA) levels, even at relatively high workloads. The elevated NEFA levels are in line with the notion that pyruvate competes with endogenously produced fatty acids for oxidative energy production. After 45 min of global ischemia pyruvate was found (a) to affect markedly the relative contribution of ATP, ADP and AMP to the total adenine nucleotide content and (b) to stimulate the degradation of glycogen and to enhance the accumulation of lactate, suggesting enhanced anaerobic ATP production. After restoration of flow pyruvate reduced the incidence of fibrillation and markedly improved recovery of cardiac output at both normal and high workload. Pyruvate did neither attenuate the release of lactate dehydrogenase, a marker for cell death, nor improve the conservation of the total adenine nucleotide and ATP content of hearts reperfused for 30 min. The latter findings indicate that hemodynamic recovery during reperfusion in the presence of pyruvate is neither related to the absolute tissue content of ATP nor to a reduction of irreversible cell damage, and suggest that pyruvate exerts its advantageous hemodynamic effects rather by improving the condition of reversibly damaged cells during reperfusion.
在本研究中，评估了向灌注有11 mM葡萄糖的短暂缺血离体工作大鼠心脏中添加5 mM丙酮酸作为共底物时的血流动力学和代谢效应。在2小时的常氧灌注期间，即使在相对较高的工作负荷下，丙酮酸也改善了功能稳定性，防止了糖原和三酰甘油储备的消耗，并提高了非酯化脂肪酸（NEFA）水平。升高的NEFA水平与丙酮酸与内源性产生的脂肪酸竞争氧化能量产生的观点一致。在全心缺血45分钟后，发现丙酮酸（a）显著影响ATP、ADP和AMP对总腺嘌呤核苷酸含量的相对贡献，（b）刺激糖原降解并增强乳酸积累，提示无氧ATP产生增加。恢复血流后，丙酮酸降低了颤动发生率，并在正常和高工作负荷下均显著改善了心输出量的恢复。丙酮酸既未减弱作为细胞死亡标志物的乳酸脱氢酶的释放，也未改善再灌注30分钟心脏的总腺嘌呤核苷酸和ATP含量的保存。后一发现表明，丙酮酸存在时再灌注期间的血流动力学恢复既与ATP的绝对组织含量无关，也与不可逆细胞损伤的减少无关，并提示丙酮酸通过改善再灌注期间可逆性受损细胞的状况发挥其有利的血流动力学效应。
