LONG-TERM INHIBITION OF Na~+/H~+ EXCHANGE ATTENUATES CARDIAC REMODELING AFTER MYOCARDIAL INFARCTION IN RATS

Objective: In addition to pH regulation, Na\++/H\++ exchanger (NHE) has been shown to facilitate cell growth and proliferation. However, the effects of long-term inhibition of Na\++/H\++ exchange on cardiac structural and functional remodeling post myocardial infarction (MI) are still controversial. The present study was therefore carried out to further investigate the effects of long-term treatment with cariporide, a specific inhibitor of NHE-1, on cardiac remodeling after MI in rats; Methods: Male Wistar rats that underwent coronary ligation were randomly selected for cariporide treatment starting 6 h after induction of MI or no treatment.Treatment was continued up to 6 weeks post MI, after which, the arterial, venous and left ventricular catheters were chronically implanted. Twenty-four h later, after hemodynamic signals were recorded in conscious rats, they were sacrificed and hearts were taken out for morphological examinations; Results: Cariporide treatment decreased the heart weight and heart weight to body weight ratio (both \%P\%<0.05), decreased left ventricular end-diastolic pressure (\%P\%<0.001), improved myocardial contractility (d\%P\%/d\%t\%\-\{max\}) (\%P\%<0.05) and tended to increase the survival of treated rats compared to that of untreated infarct rats; Conclusion: The results of the present study indicate that the long-term inhibition of NHE with cariporide can attenuate cardiac structural remodeling and improve left ventricular dysfunction in infarcted rats, and suggest that Na\++/H\++ exchange inhibition could be an effective therapeutic strategy for myocardial infarction-induced heart failure.