Choy I O, Schepkin V D, Budinger T F, Obayashi D Y, Young J N, DeCampli W M
Center for Functional Imaging, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
Ann Thorac Surg. 1997 Jul;64(1):94-9. doi: 10.1016/s0003-4975(97)00245-2.
The accumulation of intracellular sodium during myocardial ischemia couples an inappropriate calcium influx and depressed cardiac recovery during subsequent reperfusion. The effects of the selective sodium/ hydrogen exchange inhibitor HOE 694 are evaluated during myocardial ischemia and reperfusion.
Ten isolated rat hearts were subjected to a 2-minute infusion of St. Thomas' cardioplegia +/- 1 mumol/L HOE 694 followed by 50 minutes' normothermic (37 degrees C) global ischemia. Intracellular sodium accumulation was continuously measured using triple quantum filtered 23Na nuclear magnetic resonance spectroscopy without chemical shift reagents. Hemodynamic variables were assessed before and after ischemia.
The addition of 1 mumol/L HOE 694 to St. Thomas cardioplegic solution (n = 5) attenuated the accumulation of intracellular sodium after 50 minutes' ischemia (160.5% +/- 9.1% versus 203.4% +/- 10.9% [mean +/- standard error], HOE 694 versus control, respectively; p = 0.014) and after the initial reperfusion period (first 30 minutes) (288.7% +/- 10.2% versus 335.9% +/- 10.3%; p = 0.008). HOE 694-treated hearts showed significantly improved postischemic recovery of left ventricular developed pressure (53.5% +/- 8.4% versus 26.4% +/- 6.6%; p = 0.036) and rate-pressure product (40.2% +/- 6.9% versus 13.2% +/- 5%; p = 0.014). Postischemic recovery of coronary flow was not significantly different between the two groups (68.6% +/- 5.9% versus 55.5% +/- 4.6%, HOE 694 versus control, respectively; p = 0.11).
The addition of 1 mumol/L HOE 694 to cardioplegic solution attenuates the increase of intracellular sodium during myocardial ischemia and early reperfusion. This is coupled with an improved recovery of contractile function, possibly as a result of decreased sodium and calcium overload of ischemic myocardium.
心肌缺血期间细胞内钠的蓄积伴随着不适当的钙内流，并在随后的再灌注过程中导致心脏恢复能力下降。本研究评估了选择性钠/氢交换抑制剂HOE 694在心肌缺血和再灌注过程中的作用。
10只离体大鼠心脏先接受2分钟的圣托马斯停搏液灌注（±1 μmol/L HOE 694），随后进行50分钟的常温（37℃）全心缺血。使用无化学位移试剂的三量子滤波23Na核磁共振波谱法连续测量细胞内钠的蓄积情况。在缺血前后评估血流动力学变量。
在圣托马斯停搏液中添加1 μmol/L HOE 694（n = 5）可减轻50分钟缺血后（分别为160.5%±9.1%和203.4%±10.9%[均值±标准误]，HOE 694组与对照组相比；p = 0.014）以及初始再灌注期（最初30分钟）后（288.7%±10.2%与335.9%±10.3%；p = 0.008）细胞内钠的蓄积。HOE 694处理的心脏缺血后左心室舒张末压的恢复（53.5%±8.4%与26.4%±6.6%；p = 0.036）和心率-血压乘积（40.2%±6.9%与13.2%±5%；p = 0.014）显著改善。两组间缺血后冠脉血流的恢复无显著差异（分别为68.6%±5.9%与55.5%±4.6%，HOE 694组与对照组相比；p = 0.11）。
在停搏液中添加1 μmol/L HOE 694可减轻心肌缺血和早期再灌注期间细胞内钠的增加。这与收缩功能的改善相关，可能是缺血心肌钠和钙超载减少的结果。
