Chronic administration of carvedilol improves cardiac function in 6-month-old Syrian cardiomyopathic hamsters.

Heart failure (HF) is a multifactorial and progressive disease that has been linked to activation of the renin-angiotensin and sympathetic systems. In recent years, beta-blockers have been shown to improve the status of HF patients, although the precise mechanisms remain unclear. The present study evaluates the effect of beta-blockade with carvedilol (1 mg/kg/day) on cardiovascular function in 2- and 6-month-old cardiomyopathic hamsters (SCH) after 1-month and 5-month treatment periods with the drug, respectively. Age-matched golden hamsters were used as controls (CT). Systolic blood pressure (SBP) and echocardiographic studies were evaluated. The latter studies included left ventricular end-systolic (LVESV) and end-diastolic (LVEDV) volumes, ejection fraction (EF), cardiac output index (COI), heart rate (HR), and left ventricular posterior wall thickness (LVPWT). In 2-month-old SCH, carvedilol administration during a 1-month period reduced SBP from 107.59 +/- 3.49 to 77.26 +/- 3.49 mm Hg (n = 5, p < 0.05). At this stage, cardiac parameters in SCH were similar to those of controls and were not affected by carvedilol administration. In 6-month-old SCH, 5-month administration of carvedilol decreased SBP from 102.16 +/- 3.61 to 90.60 +/- 2.80 mm Hg (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 or LVPWT. These results reveal that carvedilol significantly improves cardiac function in 6-month-old cardiomyopathic hamsters, but it does not prevent ventricular dilatation. Improved cardiac function appears to be secondary to decreased total peripheral resistance, due mainly to the vasodilator properties of the drug. Thus, overactivation of the sympathetic system is not likely to be a determining factor in the etiology of dilated cardiomyopathy in this animal model.