title: 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.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Friedrich Schiller University, 07740 Jena, Germany. stefan.betge@med.uni-jena.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Betge
authors.forename: Katharina
authors.initials: K
authors.lastname: Lutz
authors.forename: Martin
authors.initials: M
authors.lastname: Roskos
authors.forename: Hans-Reiner
authors.initials: HR
authors.lastname: Figulla
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002908:Chronic Disease; D003094:Collagen / Q000032:analysis; D006333:Heart Failure / Q000401:mortality*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D017202:Myocardial Ischemia / Q000401:mortality*; D009206:Myocardium / Q000737:chemistry; D011341:Probucol / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D015996:Survival Rate; D020257:Ventricular Remodeling
chemical_list: D000975:Antioxidants; D003094:Collagen; D011341:Probucol