Myocardial protection by amiloride, a Na[+]-H[+] exchange blocker, after in vivo resuscitation of hemorrhagic shock in rats

ABSTRACT

Hemorrhagic shock and resuscitation is known to result in moyocardial contractile dysfunction and failure, but the role of the Na[+]-H[+] exchanger in hemorrhagic shock remains unclear. However, there has been intensive research investigating the myocardial protective effects on the Na[+]-H[+] exchange blockers in ischemia-reperfusion. Prior studies in our laboratory found that blocking the Na[+]-H[+] exchanger for short period on an ex vivo perfusion of isolated hearts has a protective effect on myocardial contractile function. The present study examined the protective effects of blocking the cardiac Na[+]-H[+] exchanger, by injecting 100 microM amiloride intra-arterially, on myocardial contractile function after in vivo resuscitation following our hour of hemorrhagic shock in rats. Male Sraque-Dawley rats were assigned to either hemorrhagic-treated, untreated, or similar time-matched control groups [n= 4 per group]. The left carotid artery was cannulated for blood pressure monitoring and hemorrhaging. Rats were hemorrhaged using a reservoir model. Arterial blood pressure was maintained at a mean arterial blood pressure of 40 mm Hg. After a 60-min hemorrhagic shock, rats were treated or not by injection of 1 ml of 100 microM amiloride [0.027 mg/ml] intra-arterially. Rats were then resuscitated in vivo and monitored for 30 min. Hearts were harvested and perfused in the Langendorff system for 60 min for measurement of hemodynamic function. Inhibition of the Na[+]-H[+] exchanger by injecting amiloride i.a. before in vivo resuscitation following hemorrhagic shock improved myocardial contractile function. Blocking the Na[+]-H[+] exchanger using amiloride before in vivo resuscitation following hemorrhagic shock protected the heart against dysfunction