Chronic Administration of Carvedilol Improves Cardiac Function in 6‐month‐old Syrian Cardiomyopathic Hamsters.

Abstract

Heart failure (HF) is a multifactorial disease that has been linked to activation of the sympathetic system. β-blockers improve the status of HF patients, but the precise mechanisms remain unclear. This study evaluates the effect of carvedilol (1mg/kg/day) on cardiac function of 2- and 6-month-old cardiomyopathic hamsters (SCH) after 1 and 5 months of treatment with the drug. Systolic blood pressure (SBP), left ventricular end-systolic and -diastolic volumes ((LVESV, LVEDV), ejection fraction (EF), cardiac output index (COI), heart rate (HR), and posterior wall thickness (LVPWT) were evaluated. In 2-month-old SCH, carvedilol reduced SBP from 108 ± 3 to 77 ± 3 mmHg, (n=5, P<0.05). At this stage, cardiac parameters in SCH were similar to those of controls and were not affected by the drug. In 6-month-old SCH, carvedilol decreased SBP from 102± 4 to 90 ± 3 mmHg (n=5, P<0.05), HR (from 363±14 to 324±14 bpm, n=5, P<0.05), and LVESV ( from 0.18±0.01 to 0.13±0.01 ml/100 g BW, n=5, P<0.05), and increased EF and COI by 14%, and 23% respectively (n=5, P<0.05). The drug did not modify LVEDV and LVPWT. Carvedilol significantly improves cardiac function in 6-month-old SCH, but it does not fully prevent ventricular dilatation. Thus, overactivation of the sympathetic system is not likely to be a determining factor in the etiology of dilated cardiomyopathy in this animal model. Supported by NIH Grant 2 SO6 GM08224 MBRS-SCORE.