Oral treatment with probucol in a pharmacological dose has no beneficial effects on mortality in chronic ischemic heart failure after large myocardial infarction in rats

Cardiac remodeling after myocardial infarction is in part triggered and maintained by reactive oxygen species. Antioxidants such as probucol have shown positive short-term effects on these cardiac interstitial changes in different experimental models after intraperitoneal administration or after per-oral administration with a long pre-treatment period or in high doses. In this study, the long-term effects on mortality and cardiac remodeling were examined after induction of a large myocardial infarction in a clinical daily-life-like setting. Male Lewis rats were randomized to the study groups. Large anterolateral myocardial infarctions were induced or sham operations performed. The oral treatment was started after 48 h either with probucol or placebo after myocardial infarction and with placebo after sham operation. Induction of large myocardial infarctions led to changes of the left ventricular stiffness constants, a dilatation of the left ventricle and an increased interstitial fibrosis in the remote non-infarcted part. These changes were in tendency, but not significantly, reversed after treatment with probucol. The 6-month survival rates were 53.1% in the group probucol-myocardial infarction, 43.2% in the group placebo-myocardial infarction and 100% in the group after sham operation. There were no significant differences at Kaplan-Meier analysis between the groups after myocardial infarctions. Oral treatment with the antioxidant probucol started after myocardial infarction in a pharmacological dose does not have favourable effects on the long-term mortality in the chronic ischemic heart failure model in the rat. (c) 2006 Elsevier B.V. All rights reserved.