Lab Anim Res.  2010 Mar;26(1):75-82. 10.5625/lar.2010.26.1.75.

Comparing the Effects of Carvedilol Enantiomers on Regression of Established Cardiac Hypertrophy Induced by Pressure Overload

• Hao J
• Kim CH

• KMID: 1458943
• DOI: http://doi.org/10.5625/lar.2010.26.1.75

Abstract

Pressure overload diseases such as valvular stenosis and systemic hypertension morphologically manifest in patients as cardiac concentric hypertrophy. Preventing cardiac remodeling due to increased pressure overload is important to reduce the morbidity and mortality. A recent clinical study has shown that carvedilol has beneficial effects on the survival rate of patients with heart failure. This may be due to the actions of carvedilol such as beta-adrenoceptor blockade and the alpha1-adrenergic receptor blockade effects. Therefore, we investigated whether carvedilol can reverse preexisting cardiac hypertrophy and we compared the effects of racemic carvedilol and the carvedilol enantiomers. Cardiac hypertrophy was induced in rats by suprarenal transverse abdominal aortic constriction (AC). Fifteen weeks after AC surgery, concentric hypertrophy was identified in the AC group by performing echocardiography. Low dose S- and SR-carvedilol (2 mg/kg/day), which were orally administered for three weeks, caused significant regression of the cardiac hypertrophy, and this most significantly occurred in the rats that received S-carvedilol. However, R-carvedilol did not reduce cardiac hypertrophy. Regression of cardiac hypertrophy by carvedilol was confirmed on the echocardiograms and electrocardiograms. These results suggest that carvedilol could reverse the development of leftventricular concentric hypertrophy that is induced by pressure overload. S-carvedilol is proposed to be superior to SR-and R-carvedilol as a beneficial treatment for cardiac hypertrophy.

Keyword

Established cardiac hypertrophy; carvedilol; enantiomers; pressure overload

MeSH Terms

Animals
Carbazoles
Cardiomegaly
Constriction
Constriction, Pathologic
Echocardiography
Electrocardiography
Heart Failure
Humans
Hypertension
Hypertrophy
Propanolamines
Rats
Survival Rate
Carbazoles
Propanolamines

Figure

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  Figure 1. Experimental design. Cardiac hypertrophy were confirmed at 15 weeks after abdominal aortic constriction (AC) using echocardiography. Carvedilol was dissolved in 0.5% methylcellulose and oral administered (1 mL/kg) for 3 weeks. Cardiac function, cardiac hypertrophy and electrocardiogram were performed after 18 weeks of abdominal AC.

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  Figure 2. Regression of pressure overload induced cardiac hypertrophy in vivo by carvedilol. A. Representative hearts of rats treated with 18 weeks aortic constriction (AC) or 15 weeks AC+carvedilol for 3 weeks. bar=1 mm. B. Heart wet weight was normalized to body weight in each rat as an index of cardiac hypertrophy. Heart weight to body weight ratio was reversed by 2 mg/ kg/d carvedilol in hypertrophied heart induced by aortic constriction (AC). C. Liver weight to body weight ratio. R, R-carvedilol; SR, SR-carvedilol; S, S-carvedilol. †,#P<0.001 compared with sham; ∗P<0.001 compared with AC, n≥6.

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  Figure 3. Representative M-mode echocardiograms after 3 weeks of carvedilol administration in established cardiac hypertrophy induced by 15 weeks of aortic constriction (AC). Quantitative data are shown in Table 1. Concentric cardiac remodeling was observed in the AC group. The increased wall thickness was reversed by S-carvedilol. R, R-carvedilol; SR, SR-carvedilol; S, S-carvedilol.

• 

  Figure 4. Representative electrocardiograms after 3 weeks of carvedilol administration in established cardiac hypertrophy induced by 15 weeks of aortic constriction (AC). Quantitative data are shown in Table 3. Abnormal ECGs were observed in the AC group and these wave were significantly reversed by S-carvedilol. R, R-carvedilol; SR, SR-carvedilol; S, S-carvedilol.

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