Spironolactone improves the arrhythmogenic substrate in heart failure by preventing ventricular electrical activation delays associated with myocardial interstitial fibrosis and inflammation.

摘要: MR Blockade Reduces Electrical Delays and Fibrosis  Introduction Mineralocorticoid receptor antagonism reduces sudden cardiac death in heart failure, but the underlying mechanism is unclear. Our previous studies indicate that treatment with a mineralocorticoid antagonist prevents adverse ventricular electrophysiological remodeling tachyarrhythmia inducibility rapid pacing-induced failure model. This study's aim was to determine whether chronic spironolactone formation of local electrical activation delays cardiomyopathic ventricle by attenuating inflammatory pathways myocardial fibrosis. Methods Results Dogs subjected pacing at 220 bpm for 5 weeks absence or presence were assessed echocardiography, electrophysiology study, fibrosis measurements cytokine mRNA expression analysis. Spironolactone failed prevent LV systolic dysfunction chamber enlargement dogs underwent pacing. prevented electrogram widening after premature stimulation short coupling intervals, fractionation, interstitial fibrosis, (interleukin-6, tumor necrosis factor-α) gene overexpression paced failure. Conclusions Our findings establish an important link between expression, during excitation provide insight into mechanisms which may development arrhythmogenic substrate failure.