Maddaford T G, Pierce G N
Ion Transport Laboratory, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Am J Physiol. 1997 Nov;273(5):H2232-9. doi: 10.1152/ajpheart.1997.273.5.H2232.
Amiloride analogs block Na+/H+ exchange and thereby protect the heart from myocardial ischemia-reperfusion injury. It is unclear whether drugs must be present before ischemia to be cardioprotective. After 60 min of global ischemia in the coronary-perfused right ventricular wall (RVW), as little as 1 min of exposure to dimethyl amiloride (DMA) immediately at the time of reperfusion protected the RVW. Delaying the drug attenuated the cardioprotection. If DMA was introduced in an ischemic solution near the end of ischemia, the cardioprotective effects were augmented. If the drug was washed out of the RVW vascular space before ischemia, cardioprotection was not observed. In contrast, in whole hearts, preischemic perfusion of the drug was necessary for cardioprotection and the cardioprotection remained even if the drug was washed out before ischemia. We conclude that Na+/H+ exchange is active and contributes to contractile dysfunction during the first seconds of reperfusion. This is difficult to detect in the perfused whole heart, and the washout data suggest that this may be due to a limitation in drug delivery across the vascular wall. The data also suggest that the exchanger is not as active during ischemia itself as it is during reperfusion.
氨氯吡咪类似物可阻断Na⁺/H⁺交换，从而保护心脏免受心肌缺血 - 再灌注损伤。目前尚不清楚药物是否必须在缺血前存在才能发挥心脏保护作用。在冠状动脉灌注的右心室壁（RVW）进行60分钟全心缺血后，再灌注时立即暴露于二甲基氨氯吡咪（DMA）仅1分钟就能保护RVW。延迟给药会减弱心脏保护作用。如果在缺血接近结束时将DMA加入缺血溶液中，心脏保护作用会增强。如果在缺血前将药物从RVW血管间隙中冲洗掉，则未观察到心脏保护作用。相比之下，在完整心脏中，缺血前灌注药物对于心脏保护是必要的，并且即使在缺血前将药物冲洗掉，心脏保护作用仍然存在。我们得出结论，Na⁺/H⁺交换在再灌注的最初几秒内是活跃的，并导致收缩功能障碍。这在灌注的完整心脏中很难检测到，冲洗数据表明这可能是由于药物跨血管壁递送的限制所致。数据还表明，该交换体在缺血期间本身不如在再灌注期间活跃。
