Atrial remodeling in an ovine model of anthracycline-induced nonischemic cardiomyopathy: Remodeling of the same sort

Dennis H. Lau, Peter J. Psaltis, Lorraine MacKenzie, Darren J. Kelly, Angelo Carbone, Michael Worthington, Adam J. Nelson, Yuan Zhang, Pawel Kuklik, Christopher X. Wong, James Edwards, David A. Saint, Stephen G. Worthley, Prashanthan Sanders

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Atrial Remodeling in Doxorubicin Cardiomyopathy. Introduction: All preclinical studies of atrial remodeling in heart failure (HF) have been confined to a single model of rapid ventricular pacing. To evaluate whether the atrial changes were specific to the model or represented an end result of HF, this study aimed to characterize atrial remodeling in an ovine model of doxorubicin-induced cardiomyopathy. Methods and Results: Fourteen sheep, 7 with cardiomyopathy induced by repeated intracoronary doxorubicin infusions and 7 controls, were studied. The development of HF was monitored by cardiac imaging and hemodynamic parameters. Open chest electrophysiological study was performed using custom-made 128-electrode epicardial plaque assessing effective refractory period (ERP) and conduction velocity. Atrial tissues were harvested for structural analysis. The HF group had demonstrable moderate global HF (left ventricular ejection fraction [LVEF]: 37.1 vs 46.4%; P = 0.003) and showed the following compared to controls: left atrial dilatation (P = 0.02) and dysfunction (P = 0.005); longer P-wave duration (P < 0.05); higher ERP at all cycle lengths (P ≤ 0.002) and locations (P < 0.001); slower conduction velocity (P < 0.001); increased conduction heterogeneity index (P < 0.001); increased atrial fibrosis (right atrial [RA]: 5.9 ± 2.6 vs 2.8 ± 0.9%; P < 0.0001, left atrial [LA]: 3.7 ± 2.2 vs 2.4 ± 1.1%; P = 0.002), and longer induced atrial fibrillation (AF) episodes (16 ± 22 vs 2 ± 3 seconds; P = 0.04). Conclusion: In this model of HF, there was significant atrial remodeling characterized by atrial enlargement/dysfunction, increased fibrosis, slowed/heterogeneous conduction, and increased refractoriness associated with more sustained AF. These findings appear the "same sort" to previous models of HF implicating a final common substrate leading to the development of AF in HF.

Original languageEnglish
Pages (from-to)175-182
Number of pages8
JournalJournal of Cardiovascular Electrophysiology
Volume22
Issue number2
DOIs
Publication statusPublished or Issued - 1 Feb 2011

Keywords

  • atrial fibrillation
  • cardiomyopathy
  • electrophysiology
  • heart failure
  • remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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