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

Victor P. Long, Ingrid M. Bonilla, Pedro Vargas-Pinto, Yoshinori Nishijima, Arun Sridhar, Chun Li, Kent Mowrey, Patrick Wright, Murugesan Velayutham, Sanjay Kumar, Nam Y. Lee, Jay L. Zweier, Peter J. Mohler, Sandor Györke, Cynthia A. Carnes

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Aims 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 4-6 weeks 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. Main methods HF was induced by ventricular tachypacing for one (short-term) or four (chronic) months to study remodeling. Key findings Left ventricular contractility was progressively reduced, while ventricular hypertrophy and interstitial fibrosis were evident at 4 month but not 1 month of HF. Left ventricular myocyte action potentials were prolonged after 4 (p < 0.05) but not 1 month of HF. Repolarization instability and early afterdepolarizations were evident only after 4 months of HF (p < 0.05), coinciding with a prolonged QTc interval (p < 0.05). The transient outward potassium current was reduced in both HF groups (p < 0.05). The outward component of the inward rectifier potassium current was reduced only in the 4 month HF group (p < 0.05). The delayed rectifier potassium currents were reduced in 4 (p < 0.05) but not 1 month of HF. Reactive oxygen species were increased at both 1 and 4 months of HF (p < 0.05). Significance Reduced Ito, outward IK1, IKs, and IKr in HF contribute to EAD formation. Chronic, but not short term canine HF, results in the altered electrophysiology and repolarization instability characteristic of end-stage human HF.

Original languageEnglish (US)
Pages (from-to)61-71
Number of pages11
JournalLife Sciences
StatePublished - Feb 15 2015


  • Electrophysiology
  • Fibrosis
  • Heart failure
  • Hypertrophy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)


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