Long-term inhibition of Na+/H+ exchange attenuates cardiac remodeling after myocardial infarction in rats

Objective: In addition to pH regulation, Na + /H + exchange (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.