Inhibition of Na+–H+ exchange before resuscitation following hemorrhagic shock is cardioprotective in rats

Background: Stimulation of the Na+–H+ exchanger during resuscitation following hemorrhagic shock results in myocardial injury and dysfunction. Inhibition of the Na+–H+ exchanger appears to be a new pharmacological tool for myocardial protection following ischemia– reperfusion. Our lab showed that inhibition of the Na+–H+ exchanger, using amiloride and dimethyl amiloride, before ex vivo resuscitation of isolated perfused hearts protected the myocardium and improved the post-resuscitation myocardial function. The purpose of the present study was to examine the myocardial protective effects of treating the hemorrhagic shocked rats by intra-arterial injection of 20 lMdimethyl amiloride (DMA), a specific Na+–H+ exchanger blocker, before in vivo resuscitation. Methods: Sprague–Dawley rats were assigned to hemorrhagic treated or untreated groups (n= 4 per group). After 60 min of hemorrhagic shock, rats were treated or not by injection of 20 lM 5- (N,N-dimethyl)-amiloride (DMA) intra-arterially. Rats were then resuscitated in vivo and monitored for 30 min. Then hearts were harvested and perfused in the Langendorff system for 60 min for measurements of hemodynamic function. Results: Administration of DMA before in vivo resuscitation following 60 min of hemorrhagic shock and 30 min of in vivo resuscitation, 20 lM DMA intra-arterially significantly improved post-resuscitation myocardial function.Conclusion: Our results suggest that DMA protects the heart against post-resuscitation myocardialinjury.