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or more than 20 years, anthracycline antibiotics have been used as major anticancer drugs. However, their cardiotoxicity has limited their usage. 1 Clinically, there are 2 types of cardiotoxicity. One type occurs rapidly after a single dose of anthracycline and is characterized by electrocardiographic changes, arrhythmias and a reversible decrease in ventricular contractile function. 2 The other type of cardiotoxicity is characterized by irreversible deterioration of ventricular contractile function, leading to congestive heart failure; it is directly related to the cumulative anthracycline dose. In patients with a cumulative doxorubicin dose of 430-600 mg/m 2 , the prevalence of ventricular contractile dysfunction is 60%. 3 However, we have shown that cardiac function deterioration could already be detected with exercise stress testing at a cumulative dose of 175 mg/m 2 . 4 Uchikoba et al suggested that signal-averaged electrocardiogram abnormalities appeared after a single dose of anthracycline. 5 These reports suggest that anthracycline cardiotoxicity develops silently with the first dose, and cardiac dysfunction becomes clinically significant at a cumulative dose of approximately 430-600 mg/m 2 .Among the proposed mechanisms by which anthracy- Circulation Journal Vol.71, November 2007clines cause irreversible myocardial injury, redox cycling of anthracycline is the most likely. 6 The quinone moiety of the anthracycline is known to act as a catalyst for the formation of reactive oxygen species, including superoxide anion and hydrogen peroxide. The unique sensitivity of the myocardium to anthracyclines may be due to the low levels of catalase and superoxide dismutase (SOD) that are found in cardiac myocytes. 7 Recently, edaravone, a potent free radical scavenger, was clinically used to reduce neuronal damage following ischemic stroke. 8 Edaravone quenches the hydroxyl radical (·OH), and has inhibitory effects on peroxynitrite (ONOO-) and both water-soluble and lipid-soluble peroxyl radicals (LOO·). 9 Based on these data, we hypothesized that edaravone would protect cardiomyocytes against anthracycline cytotoxicity. To test our hypothesis, we used rat neonatal cardiac myocytes to examine myocardial cell death caused by daunorubicin in vitro; we also examined cardiac function in vivo. MethodsThe investigation conformed with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996). And all protocols were approved by the Animal Studies Committee at Nippon Medical School Background It was investigated whether edaravone, a potent free radical scavenger, would protect against anthracycline-induced cardiotoxicity and prevent cardiac function deterioration. Methods and ResultsCultured neonatal rat cardiomyocytes were stimulated by daunorubicin 1 mol/L either with or without edaravone or superoxide dismutase mimetic Mn (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP). Cell viability was estimated by measuring t...

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Background: New antiviral drugs can rapidly improve the symptoms of influenza, but

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