Chronic imipramine treatment as a rodent model for congestive heart failure

Previous investigators have demonstrated that chronic administration of tricyclic antidepressants downregulates brain β-adrenergic receptor density. The purpose of this study was to investigate the effect of chronic administration of the tricyclic antidepressant, imipramine (IMI), on cardiac β-adrenergic receptor binding characteristics and heart function. IMI (15 mg/kg, i.p.) or vehicle were administered twice daily for 14 days to adult rats. Food intake, water intake, and body weight decreased in IMI-treated rats. Plasma norepinephrine (NE) levels were increased in IMI-treated rats compared to control (IMI: 40 ± 3; vehicle. 26 ± 3 ng/ml, P < 0.05). Radioligand binding analysis in LV membranes using the nonselective ligand [¹²⁵I]Iodocyanopindolol (ICYP) demonstrated no alterations in the affinity or density of cardiac β-adrenergic receptors. Echocardiographic (Echo) analysis coupled with examination of left ventricle (LV)/body weight ratio, demonstrated that chronic IMI-treatment did not alter LV mass. Echo analysis also demonstrated a progressive increase in mean systolic diameter in IMI-treated rats, accompanied by a marked decrease in degree of fractional shortening < 0.05). These results suggest that chronic IMI-treatment results in compromised cardiac function and may serve as a useful rodent model for heart failure. (Graph Presented).