Title

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

DOI

https://doi.org/10.1016/j.lfs.2014.12.024

Document Type

Article

Publication Date

2-15-2015

Publication Title

Life Sciences

Abstract

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 I , outward I , I , and I 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. to K1 Ks Kr

Volume

123

First Page

61

Last Page

71

ISSN

00243205

PubMed ID

25596015

Identifier

SCOPUS_ID:84921651637

Documento original

Compartir

COinS