Heart failure duration progressively modulates the arrhythmia substrate through structural and electrical remodeling

• Published in: Life sciences (1973) 2015-02, Vol.123, p.61-71
• Main Authors: Long, Victor P., Bonilla, Ingrid M., Vargas-Pinto, Pedro, Nishijima, Yoshinori, Sridhar, Arun, Li, Chun, Mowrey, Kent, Wright, Patrick, Velayutham, Murugesan, Kumar, Sanjay, Lee, Nam Y., Zweier, Jay L., Mohler, Peter J., Györke, Sandor, Carnes, Cynthia A.
• Format: Article
• Language: English
• Subjects: Action Potentials - physiology; Amphotericin B; Analysis of Variance; Animals; Arrhythmias, Cardiac - complications; Delayed Rectifier Potassium Channels - metabolism; DNA Primers - genetics; Dogs; Electrocardiography; Electron Spin Resonance Spectroscopy; Electrophysiology; Fibrosis; Heart failure; Heart Failure - etiology; Heart Failure - physiopathology; Hypertrophy; Immunoblotting; Myocardial Contraction - physiology; Patch-Clamp Techniques; Potassium Channels, Inwardly Rectifying - metabolism; Reactive Oxygen Species - metabolism; Real-Time Polymerase Chain Reaction; Time Factors; Ventricular Remodeling - physiology
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2014.12.024

Ventricular arrhythmias are a common cause of death in patients with heart failure (HF). Structural and electrical abnormalities in the heart provide a substrate for such arrhythmias. Canine tachypacing-induced HF models of 4–6weeks duration are often used to study pathophysiology and therapies for HF. We hypothesized that a chronic canine model of HF would result in greater electrical and structural remodeling than a short term model, leading to a more arrhythmogenic substrate. HF was induced by ventricular tachypacing for one (short-term) or four (chronic) months to study remodeling. Left ventricular contractility was progressively reduced, while ventricular hypertrophy and interstitial fibrosis were evident at 4month but not 1month of HF. Left ventricular myocyte action potentials were prolonged after 4 (p