© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Antioxidants attenuate myocyte apoptosis in the remote non-infarcted myocardium following large myocardial infarction
Department of Internal Medicine, Division of Cardiovascular Diseases, University of Iowa and Veterans Administration Medical Center, Iowa City, IA 52242, USA
* Corresponding author. Present address: Cornerstone Cardiology, 721 N. Elm Street, High Point, NC 27262, USA. Tel.: +1-336-883-0402; fax: +1-336-883-4120 hoskarsson{at}hprhs.com
Objective: Increased oxidative stress and myocyte apoptosis co-exist in the remote non-infarcted myocardium (RM) following a large myocardial infarction. We proposed that these phenomena are causally related. Methods and results: On day 3 after induction of myocardial infarction, Sprague–Dawley rats were randomized to receive probucol and pyrrolidine dithiocarbamate (MI-T), or vehicle only (MI) for 7 weeks. Control rats (C) received vehicle. At 7 weeks, lipidperoxidation within the RM was assessed by measuring thiobarbituric acid reactive substances, which were significantly increased in MI vs. C, while MI-T was not different from C. There was a significant increase in cardiac myocytes positive for in situ TdT-UTP nick-end labeling within the RM in MI vs. C, which was inhibited in MI-T. Furthermore, internucleosomal DNA fragmentation was clearly demonstrated on agarose gels from RM in the MI group, while it was much less apparent on gels from RM in the C and MI-T groups. Western blot analysis showed a significant increase in p53, Bax and caspase-3 protein expression within the RM of MI vs. C, all of which were inhibited in the MI-T group. Furthermore, there was evidence for an increase in caspase-3 activity within the RM from MI vs. C, which was normalized in the MI-T group. Conclusions: Long-term treatment with the antioxidants probucol and pyrrolidine dithiocarbamate attenuates oxidative stress, myocyte apoptosis, caspase-3 like activity and the expression of p53, bax and caspase-3 within RM in rats after a large myocardial infarction.
KEYWORDS Apoptosis; Free radicals; Heart failure
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