Abstract
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
μM dimethyl amiloride (DMA), a specific Na
+–H
+ exchanger blocker, before
in vivo resuscitation.
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
μM 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.
Administration of DMA before
in vivo resuscitation following 60
min of hemorrhagic shock and 30
min of
in vivo resuscitation, 20
μM DMA intra-arterially significantly improved post-resuscitation myocardial function.
Our results suggest that DMA protects the heart against post-resuscitation myocardial injury.