This study was designed to determine the potential therapeutic effects of a new sodium-hydrogen exchanger (NHE-1) inhibitor in the rat coronary artery ligation model of chronic heart failure. After the induction of acute myocardial infarction, rats were entered randomly dosedranging from0.3 mg/kg, 1.0 mg/kg, and 3.0 mg/kg. Solid state micrometer hemodynamics, echocardiographic, and pressure-volume relationships were measured after6 weeks of treatment. Treatment with this NHE- 1 inhibitor at 3 mg/kg increased (P< 0.05) ejection fraction from 23±3% (N=6) to 33±2% (N=13) while the 1 mg/kg dose decreased (P< 0.05) the infarct size in CHF rats from 21.7±1.4% (N=7) to 15.9±0.7% (N=3) and prevented (P< 0.05) dilatation of the left ventricle in CHF rats in diastole (1.0±0.1 cm, N=6) to 0.9±0.1 cm, N=10) and in systole (0.9±0.1 cm, N=6) to 0.8±0.1, N=10). These study results suggest that this new NHE-1 inhibitor may be potentially useful in treating CHF with an improvement in maladaptive left ventricule remodeling. Because the mechanism of action of this agent is entirely different than the currently applied approach in treating CHFthat focuses on aggressive neurohormonal blockade and because this agent does not adversely affect important hemodynamic variables, further investigations with this agent may be warranted.

Keywords: Congestive heart failure; Sodium/hydrogen exchange; Cardiovascular disease; Cardiovascular drugs

Keywords: CHF: Chronic Heart Failure; NHE-1: Sodium-Hydrogen Exchanger; NCX: Sodium-Calcium Exchanger; Ca²⁺: Calcium; Na⁺: Sodium; Na⁺-K⁺ATPase: Sodium-Potassium ATPase; NKCC: Sodium-Potassium-Chloride co-transporter; MI: Myocardial Infarction; BI: Boehringer Ingelheim; LV: left Ventricle; EF: Ejection Fraction; LVD: left ventricular dysfunction; PV: Pressure-Volume; SE: Standard Error; ARB: Angiotensin Receptor Blocker ACE: Angiotensin Converting Enzyme