Bradycardic therapy improves left ventricular function and remodeling in dogs with coronary embolization-induced chronic heart failure. J Pharmacol Exp Ther 321: 469–476

Both -adrenergic blockade and bradycardia may contribute to the therapeutic effect of -blockers in chronic heart failure (CHF). This study tested the relative importance of bradycardia by comparing cilobradine (Cilo), a sinus node inhibitor, with a -blocker, metoprolol (Meto), in an established canine model of CHF. Dogs were chronically instrumented for hemodynamic and left ventricular (LV) volume measurements. CHF was cre-ated by daily coronary embolization via a chronically implanted coronary (left anterior descending coronary artery) catheter. After establishment of CHF, control (n 6), Meto (30 mg/day, n 5), Cilo (low) (1 mg/kg/day, n 5), or Cilo (high) (3 mg/kg/ day, n 5) was given orally for 12 weeks. Systemic hemody-namics, echocardiography, and pressure volume analysis were measured at baseline, at CHF, and 3 months after treatment i