The journal of physiological sciences : JPS

Dimethyl amiloride, a Na+-H+ exchange inhibitor, and its cardioprotective effects in hemorrhagic shock in in vivo resuscitated rats.

PMID 19340541


Stimulation of the Na(+)-H(+) exchanger plays an important role in the pathway of myocardial dysfunction and injury following hemorrhagic shock. Inhibition of the Na(+)-H(+) exchanger appears to be a new pharmacological tool for myocardial protection. Despite the extensive research that has been done on the role of the Na(+)-H(+) exchanger in ischemia reperfusion, little is known about the role of the exchanger following hemorrhagic shock. The purpose of this study was to examine the protective effects of blocking the cardiac Na(+)-H(+) exchanger, using 20 microM dimethyl amiloride (DMA), a specific Na(+)-H(+) exchanger blocker, on myocardial contractile function after ex vivo perfusion of isolated rat heart following 1 h of hemorrhagic shock. Sprague-Dawley rats were assigned to hemorrhage + DMA, hemorrhage, sham hemorrhage + DMA and sham hemorrhage groups (n = 6 per group). Hearts were perfused with a balanced salt solution for 60 min. In the DMA treated group, 20 microM DMA was added for the first 5 min of the 60-min ex vivo heart resuscitation. The results showed that inhibition of the Na(+)-H(+) exchanger for 5 min on ex vivo perfusion of the isolated hearts following hemorrhagic shock using 20 microM DMA improved myocardial contractile function. Blocking the Na(+)-H(+) exchanger on ex vivo perfusion of isolated hearts using 20 muM DMA has protective effects on myocardial contractile function.