Postinfarct cardiac remodeling and the substrate for sudden cardiac death: role of oxidative stress and myocardial fibrosis

“…in a heart with well-coupled myocytes, a greater number of myocytes with simultaneous early afterdepolarization and delayed afterdepolarization are required to overcome the electrotonic sink effect…” The biological changes that occur after myocardial infarction (MI) produce gross structural abnormalities in the heart, such as scar tissue, hypertrophy and chamber dilatation, which may be followed by functional deterioration and the clinical symptoms of heart failure or ventricular arrhythmia. Heart failure is a well-known risk factor for ventricular arrhythmia that is associated with significantly higher car diovascular mortality. It may be too late to cure a dysfunctional heart. Therefore, understanding the molecular mechanisms and signaling pathways involved in postMI remodeling can provide useful insights for the very important period of time that follows infarction (the ‘golden therapeutic window’). Infarcted hearts show several important pathological changes that are arrhythmogenic, such as nerve sprouting [1], action potential duration (APD) alternans [2] and a decreased cardiac sodium current [3]. Among the underlying pathophysiologic changes, oxidative stress and myocardial fibrosis are particularly impor tant for several reasons. First, there is strong experimental and clinical evidence for their arrhythmogenicity. Second, there are potential therapeutic options to prevent them. Also, oxidative stress promotes cardiac fibrosis. Finally, oxidative stress and cardiac fibrosis potentiate the arrhyth mogenic effect of each other. This article highlights the role of oxidative stress and myocardial fibrosis in providing the sub strate for sudden cardiac death in infarcted hearts.