Chronic Administration of Carvedilol Improves Cardiac Function in 6-Month-Old Syrian Cardiomyopathic Hamsters

Abstract

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, β-blockers have been shown to improve the status of HF patients, although the precise mechanisms remain unclear. The present study evaluates the effect of β-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.

Protective effect of carvedilol against anthracycline-induced cardiomyopathy on patients with breast cancer and lymphoma

“…6 Cruz et al in a study on Hamster showed that prescription of carvedilol in 1 mg/day for each kg/day can improve heart function. 7 As we can see, above investigations has confirmed the protective effect of carvedilol in animal models. Only in 2 studies the effect of carvedilol on treatment or prevention of cardiomyopathy caused by chemotherapy has been considered.…”

Hemodynamic Alterations in the Coronary Circulation of Cardiomyopathic Hamsters: Age and Ang II–dependent Mechanisms

“…No difference in HW/BW ratios were observed for CT animals at the different ages evaluated. The reduced HW/BW ratio in CM could be related to cardiac dilation at 6 months of age 45. Intrinsic heart rates (HR) of the isolated heart were significantly lower than values reported in the literature for the retroperfused heart 39–40.…”

Chronic Treatment With N-acetylcysteine Improves Cardiac Function but Does Not Prevent Progression of Cardiomyopathy in Syrian Cardiomyopathic Hamsters

“…Our group has used the Syrian cardiomyopathic hamster (SCH) as an animal model of dilated cardiomyopathy and HF. [11][12][13][14][15][16][17] In this model, we reported significant vascular alterations in 2-month-old animals before the development of clinical manifestations of HF. These alterations include high levels of vascular ACE activity, impaired vasorelaxation in response to acetylcholine in aortic rings, and Ang II-dependent, ROSmediated, endothelial dysfunction in the coronary circulation.…”