Aussedat J, Ray A, Kay L, Verdys M, Harpey C, Rossi A
Laboratoire de Physiologie Cellulaire Cardiaque, Université Joseph Fourier, Grenoble, France.
J Cardiovasc Pharmacol. 1993 Jan;21(1):128-35. doi: 10.1097/00005344-199301000-00019.
Rat hearts, arrested in situ after intracaval injection of a simple mineral cardioplegic solution (St. Thomas), were preserved for 15 h at 4 degrees C either by simple immersion in the cardioplegic solution or low-flow perfusion by the same liquid (0.3 ml/min). Trimetazidine (TMZ) was added to the cardioplegic solution at a concentration of 10(-6) M in two additional groups corresponding to both preservation conditions. The biochemically determined ventricular ATP content was increased in immersed hearts by TMZ (+ 78%). The [ATP]/[Pi] ratio, as calculated from 31P nuclear magnetic resonance (NMR) spectroscopy, was significantly increased in both preservation conditions by TMZ: 0.08 +/- 0.03 versus 0.04 +/- 0.01 in immersed hearts and 0.53 +/- 0.13 versus 0.26 +/- 0.16 in perfused hearts (mean +/- SD). Intracellular pH was increased when TMZ was administered in perfused hearts (7.02 +/- 0.14 vs. 6.67 +/- 0.14, mean +/- SD). Functional recovery, estimated by the pressure developed by the left ventricle (intraventricular isovolumic balloon) when hearts were reperfused with a physiologic solution, was improved by TMZ in both preservation conditions: +137% in immersed hearts and +54% in perfused hearts. These results demonstrate that both the bioenergetic status of the myocardial cell and the functional capabilities of isolated, arrested, stored rat heart can be significantly improved by addition of the antiischemic drug TMZ to the preservation solution.
通过腔静脉注射一种简单的矿质心脏停搏液（圣托马斯液）使大鼠心脏原位停搏后，将其于4℃保存15小时，保存方式为单纯浸泡于心脏停搏液中或用相同液体进行低流量灌注（0.3毫升/分钟）。在另外两组对应于两种保存条件的实验中，将曲美他嗪（TMZ）以10⁻⁶ M的浓度添加到心脏停搏液中。经生化测定，TMZ使浸泡保存的心脏心室ATP含量增加（增加78%）。根据³¹P核磁共振（NMR）光谱计算得出的[ATP]/[Pi]比值，在两种保存条件下TMZ均使其显著增加：浸泡保存的心脏中，该比值从0.04±0.01增加到0.08±0.03；灌注保存的心脏中，该比值从0.26±0.16增加到0.53±0.13（平均值±标准差）。当在灌注保存的心脏中给予TMZ时，细胞内pH值升高（7.02±0.14对6.67±0.14，平均值±标准差）。当用生理溶液对心脏进行再灌注时，通过左心室产生的压力（心室内等容球囊）评估功能恢复情况，结果显示在两种保存条件下TMZ均能改善功能恢复：浸泡保存的心脏中功能恢复提高了137%，灌注保存的心脏中提高了54%。这些结果表明，在保存溶液中添加抗缺血药物TMZ可显著改善心肌细胞的生物能量状态以及离体、停搏、保存的大鼠心脏的功能能力。
