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Am J Physiol Heart Circ Physiol 273: H2232-H2239, 1997;
0363-6135/97 $5.00
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Vol. 273, Issue 5, H2232-H2239, November 1997

Myocardial dysfunction is associated with activation of Na+/H+ exchange immediately during reperfusion

Thane G. Maddaford and Grant N. Pierce

Ion Transport Laboratory, Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, and Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada R2H 2A6

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.

sodium; calcium; sodium/hydrogen exchange


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