Effects of carvedilol on left ventricular function and oxidative stress in infants and children with idiopathic dilated cardiomyopathy: a 12-month, two-center, open-label study.

OBJECTIVES: This study was conducted to determine the effects of carvedilol adjunct to standard treatment on left ventricular function (LVF), estimated as ejection fraction (EF) and fractional shortening (FS) on echocardiography, in children with idiopathic dilated cardiomyopathy (DCM). A secondary end point was to characterize the antioxidant potential of carvedilol. METHODS: Hospitalized children aged 62.5 kg) was associated with significant decreases from baseline in systolic BP (130 [4] vs 123 [3] mm Hg; P<0.05), diastolic BP (85 [4] vs 77 [4] mm Hg; P<0.05), and HR (81 [4] vs 65 [4] bpm; P<0.001) after the first month of addition to standard therapy. At 6 months, there were significant improvements from baseline in EF (37.2% [2.4%] vs 50.2% [2.3%]; P<0.001) and FS (18.37% [2.00%] vs 23.58% [0.90%]; P<0.001). Modified NYHAC class was significantly improved in 80% of children (2.9 vs 2.3; P<0.001) at 12 months. The highest dose of carvedilol (0.8 mg/kg/d in children 62.5 kg) was well tolerated in all 21 children. No serious AEs that necessitated study drug discontinuation (tiredness, headache, vomiting) were observed. At baseline, mean (SE) erythrocyte SOD activity (2781 [116] vs 2406 [102] U/g Hb; P<0.05) and GR activity (5.3 [0.3] vs 3.0 [0.2] micromol nicotinamide adenine dinucleotide phosphate [NADPH]/min/g Hb; P<0.001) were significantly higher in children with DCM who received standard therapy compared with healthy controls.CAT activity (12.7[0.9] vs 18.5 [1.0]U/g Hb; P<0.001) was significantly lower, while GSH-Px was unchanged. At 6 and 12 months of therapy, carvedilol plus standard treatment was associated with significant decreases from baseline in SOD (2516 [126] and 2550 [118], respectively, vs 2781 [116] U/g Hb; both, P<0.001) and GR (4.7 [0.3] and 4.1 [0.2], respectively, vs 5.3 [0.2] micromol NADPH/min/g Hb; P<0.05 and P<0.001) and increased CAT (16.9 [1.0] and 16.4 [0.7], respectively, vs 12.7 [0.9] U/g Hb; both, P<0.001). CONCLUSIONS: These pediatric patients with DCM treated for 12 months with carvedilol (up to 0.8 mg/kg/d in children 62.5 kg) were found to have significant improvements in LVF and symptoms of HF. Twelve months of carvedilol therapy was associated with antioxidant enzyme activities near those observed in healthy children.

Carvedilol increases copper-zinc superoxide dismutase activity in patients with acute myocardial infarction.

Balanced and coordinated antioxidant defence enzyme activities are of utmost importance for correct physiological function and for shielding against unwelcome pathological conditions. We determined the activities of copper-zinc superoxide dismutase (CuZnSOD), catalase, glutathione peroxidase and glutathione reductase in erythrocytes isolated from patients receiving different therapy (streptokinase alone or in combination with metoprolol or with carvedilol) for up to 168 hr after starting treatment for acute myocardial infarction. We observed increased CuZnSOD activity in erythrocytes isolated from patients treated with streptokinase-carvedilol (after 6, 24 and 168 hr) and in erythrocytes isolated from patients treated with streptokinase-metoprolol (after 24 hr). In addition, positive correlation between CuZnSOD and catalase activities was found in erythrocytes isolated from patients that received streptokinase-carvedilol after 168 hr. As metoprolol does not react directly with hydrogen peroxide, it would appear that combined streptokinase-metoprolol therapy exerted its effects primarily via by beta-blockade whereas combined streptokinase-carvedilol therapy appeared to function via both beta-blockade and direct antioxidant mechanisms.