Navon G, Werrmann J G, Maron R, Cohen S M
Merck Research Laboratories, Rahway, NJ 07065.
Magn Reson Med. 1994 Nov;32(5):556-64. doi: 10.1002/mrm.1910320503.
The triple quantum filtered 23Na NMR method is applied here to measure the effects of EIPA, a specific inhibitor of the Na+/H+ antiporter, on relative intracellular sodium concentrations in isolated working hearts at baseline, during ischemia, and at subsequent reperfusion. In analogy to the spectrophotometric isosbestic point, an approach is developed that defines a value of tau at which the effect of the relaxation times on the TQF signal intensities is minimized, and the signals are proportional to the sodium concentration for both ischemic and working hearts. EIPA at 1.5 microM significantly inhibited (P < 0.01) the influx of intracellular Na+ during 20 min of ischemia at 36.2 degrees C in this rat heart model. In parallel 31P NMR studies, EIPA had no effect on either the development of acidosis during ischemia or on the recovery of pHi during reperfusion despite its profound effect on intracellular Na+ influx. Thus, under our conditions the Na+/H+ antiporter did not play a critical role in the maintenance of intracellular pH. EIPA treatment resulted in improved recovery (P < 0.005) of mechanical function after 20 min of ischemia. [ATP] was higher in treated hearts during ischemia and reperfusion.
本文应用三量子滤波23Na核磁共振方法，来测量钠氢交换体特异性抑制剂EIPA对离体工作心脏在基线、缺血期间及随后再灌注时细胞内相对钠浓度的影响。类似于分光光度等吸收点，开发了一种方法来定义τ值，在该值下弛豫时间对三量子滤波信号强度的影响最小，并且对于缺血心脏和工作心脏，信号均与钠浓度成正比。在该大鼠心脏模型中，1.5微摩尔的EIPA在36.2摄氏度下显著抑制（P < 0.01）了缺血20分钟期间细胞内Na+的流入。在平行的31P核磁共振研究中，尽管EIPA对细胞内Na+流入有显著影响，但它对缺血期间酸中毒的发展或再灌注期间细胞内pH值的恢复均无影响。因此，在我们的条件下，钠氢交换体在维持细胞内pH值方面不发挥关键作用。EIPA处理使缺血20分钟后的机械功能恢复得到改善（P < 0.005）。在缺血和再灌注期间，处理过的心脏中[ATP]更高。
