Effects of cardiac Na[+]- H[+] exchange blockade on myocardial contractile function during hemorrhagic shock

ABSTRACT

Myocardial contractile dysfunction has been described following hemorrhagic shock. While the Na [+]-H[+] exchanger is well known to be a major regulator of intracellular pH. its role in hemorrhagic shock remains unclear. However, there has been intensive research investigating the myocardial protective role of several Na[+]-H[+] exchangers in ischemia-reperfusion, which is similar to hemorrhagic shock as both result in extracellular acidosis. The purpose of the present study was to examine the effects of blocking the cardiac Na[+]-H[+] exchanger, using 100 micro M. amiloride, on myocardial contractile function after ex vivo perfusion of isolated rat heart following one hour of hemorrhagic shock. Anesthetized male Sprague-Dawley rats were assigned to either hemorrhagic treated or untreated groups, or a similar time-matched control group [n=6 per group]. Rats were hemorrhaged using a reservoir model. Arterial blood pressure was monitored for one hour, and maintained at a mean arterial blood pressure of 40 mm Hg, via an intra-arterial catheter inserted into the left carotid artery. Two arterial blood samples were taken, one at baseline and another at 60 minutes of hemorrhage. These blood samples were analyzed for pH and lactate levels. Hearts were harvested and perfused either with a balanced salt solution for 60 minutes or a solution containing 100 micro M amiloride. Myocardial function was determined with a balloon- tipped catheter inserted into the left ventricle via the mitral valve. Indices of left ventricular function were measured, including left ventricular end diastolic pressure [LVEDP], left ventricular peak systolic pressure [LVPSP], coronary perfusion pressure [Pp] and left ventricular balloon volume [BV]. The left ventricular +/- dP/dt, which is the left ventricular index of contractility, was calculated. Left ventricular compliance [C] was also calculated. The results showed that inhibition of the Na[+]-H[+] exchanger for 5 minutes of ex vivo perfusion of the isolated hearts following hemorrhagic shock, improved myocardial contractile function as compared to the hemorrhage untreated hearts. The results also showed that hemorrhagic shock decreased myocardial contractile function as compared to controls. Blocking the Na[+]-H[+] exchanger for a short period on ex vivo perfusion of isolated hearts has a protective effect on myocardial contractile function. Further research is needed to investigate the exact mechanism of protection using more specific Na[+]-H[+] exchanger inhibitors