Choong Y S, Gavin J B, Armiger L C
Department of Pathology, University of Auckland School of Medicine, New Zealand.
J Mol Cell Cardiol. 1988 Nov;20(11):1043-51. doi: 10.1016/0022-2828(88)90581-0.
The effects of exogenous glutamate (20 mM) on myocardial energy metabolism and cardiac function during low-flow ischaemia and subsequent reperfusion were studied in isolated working rat hearts. Hearts were made severely ischaemic for 60 min by reducing the perfusion rate to 0.17 ml/min, and then reperfused for 30 min. Low-flow ischaemia resulted in a 50% reduction of myocardial ATP, a 70% reduction of both creatine phosphate (CP) and GTP, and a 250% rise in AMP. After reperfusion, CP was restored to normal levels but ATP and GTP remained significantly low. All hearts failed completely to recover cardiac pump function. The addition of glutamate to the perfusate during low-flow ischaemia had no significant effect on myocardial high-energy phosphates (HEP) but slightly increased succinate production. Subsequent reperfusion without added glutamate resulted in the recovery of 62% of pre-ischaemic aortic flow rate, as well as restoration of myocardial ATP and GTP to 70% of their control values and of creatine phosphate to supranormal levels. Reperfusion with added glutamate did not raise HEP levels any further but did increase recovery of cardiac function to 92% or more of pre-ischaemic values. Thus, by mechanism(s) which are not yet clear but which may include an increase in HEP via anaerobic succinate production, elevated levels of exogenous glutamate exert a highly beneficial effect on the post-ischaemic recovery of cardiac function.
在离体工作大鼠心脏中,研究了外源性谷氨酸(20 mM)在低流量缺血及随后再灌注期间对心肌能量代谢和心脏功能的影响。通过将灌注速率降至0.17 ml/min,使心脏严重缺血60分钟,然后再灌注30分钟。低流量缺血导致心肌ATP减少50%,磷酸肌酸(CP)和GTP均减少70%,AMP升高250%。再灌注后,CP恢复到正常水平,但ATP和GTP仍显著降低。所有心脏均完全未能恢复心脏泵功能。在低流量缺血期间向灌注液中添加谷氨酸对心肌高能磷酸化合物(HEP)无显著影响,但略微增加了琥珀酸的生成。随后在不添加谷氨酸的情况下进行再灌注,可使缺血前主动脉流速恢复62%,心肌ATP和GTP恢复到对照值的70%,磷酸肌酸恢复到超正常水平。添加谷氨酸进行再灌注并未进一步提高HEP水平,但确实使心脏功能恢复到缺血前值的92%或更高。因此,通过尚不清楚但可能包括通过无氧琥珀酸生成增加HEP的机制,外源性谷氨酸水平升高对缺血后心脏功能的恢复具有高度有益的作用。