JScholar Publishers Development of a Novel Sodium-Hydrogen Exchanger Inhibitor for Heart Failure

This study was designed to determine the potential therapeutic effects of a new sodium-hydrogen exchanger (NHE-1) in-hibitor in the rat coronary artery ligation model of chronic heart failure. After the induction of acute myocardial infarc-tion, rats were entered into a randomly designed pilot dose study from 0.3 mg/kg, 1.0 mg/kg, and 3.0 mg/kg. Solid state micrometer hemodynamics, echocardiographic, and pressure-volume relationships were measured after 6 weeks of treat-ment. 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) dilata¬tion 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 ventricle remodeling. Because the mechanism of action of this agent is entirely different than the currently applied approach in treating CHF that focuses on aggressive neuro-hormo-nal blockade and because this agent does not adversely affect important hemodynamic variables, further investigations with this agent may be warranted