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


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).


CONCLUSIONS
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.
Lau
Dennis H
DH
Cardiovascular Research Centre, Departments of Cardiology and Cardiothoracic Surgery, Royal Adelaide Hospital and the Disciplines of Medicine and Physiology, University of Adelaide, Adelaide, Australia.
Psaltis
Peter J
PJ
Mackenzie
Lorraine
L
Kelly
Darren J
DJ
Carbone
Angelo
A
Worthington
Michael
M
Nelson
Adam J
AJ
Zhang
Yuan
Y
Kuklik
Pawel
P
Wong
Christopher X
CX
Edwards
James
J
Saint
David A
DA
Worthley
Stephen G
SG
Sanders
Prashanthan
P
D000818:Animals; D018943:Anthracyclines; D009202:Cardiomyopathies / Q000139:chemically induced / Q000503:physiopathology; D004195:Disease Models, Animal; D004317:Doxorubicin; D006325:Heart Atria / Q000503:physiopathology*; D006329:Heart Conduction System / Q000503:physiopathology*; D006333:Heart Failure / Q000139:chemically induced* / Q000503:physiopathology*; D006801:Humans; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000503:physiopathology; D012756:Sheep
D018943:Anthracyclines; D004317:Doxorubicin