Antioxidant vitamins attenuate oxidative stress and cardiac dysfunction intachycardia-induced cardiomyopathy

OBJECTIVES We administered antioxidant vitamins to rabbits with pacing-indu ced cardiomyopathy to assess whether antioxidant therapy retards the progre ssion of congestive heart failure (CHF). BACKGROUND Although oxidative stress is increased in CHF, whether progressi on of heart failure could be prevented or reduced by antioxidants is not kn own. METHODS Rabbits with chronic cardiac pacing and sham operation were randomi zed to receive a combination of beta-carotene, ascorbic acid and alpha-toco pherol, alpha-tocopherol alone or placebo over eight weeks. Echocardiograph y was used to measure cardiac function weekly. Resting hemodynamics and in vivo myocardial beta-adrenergic responsiveness were studied at week 8. Anim als were then sacrificed for measuring myocardial beta-receptor density, no repinephrine (NE) uptake-1 site density, sympathetic neuronal marker profil es, tissue-reduced glutathione/oxidized glutathione (GSH/GSSG) ratio and ox idative damage of mitochondrial DNA (mtDNA). RESULTS Rapid cardiac pacing increased myocardial oxidative stress as evide nced by reduced myocardial GSH/GSSG ratio and increased oxidized mtDNA and produced cardiac dysfunction, beta-adrenergic subsensitivity, beta-receptor downregulation, diminished sympathetic neurotransmitter profiles and reduc ed NE uptake-1 carrier density. A combination of antioxidant vitamins reduc ed the myocardial oxidative stress, attenuated cardiac dysfunction and prev ented myocardial beta-receptor downregulation and sympathetic nerve termina l dysfunction. Administration of alpha-tocopherol alone produced similar ef fects, but the effects were less marked than those produced by the three vi tamins together. Vitamins produced no effects in sham-operated animals. CONCLUSIONS Antioxidant vitamins reduced tissue oxidative stress in CHF and attenuated the associated cardiac dysfunction, beta-receptor downregulatio n and sympathetic nerve terminal abnormalities. The findings suggest that a ntioxidant therapy may be efficacious in human CHF. (C) 2001 by the America n College of Cardiology.