CLINICAL RESEARCH: HEART FAILURE
The cardiac atria are chambers of active remodeling and dynamic collagen turnover during evolving heart failure
Anjum Khan, MSc*,
Gordon W. Moe, MD, FACC*,
Nafiseh Nili, PhD*,
Effat Rezaei, PhD*,
Muhammad Eskandarian, MD*,
Jagdish Butany, MD and
Bradley H. Strauss, MD, PhD, FACC*,*
* Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Center, St. Michael's Hospital, Toronto, Ontario, Canada
University Health Network, University of Toronto, Toronto, Ontario, Canada
Manuscript received February 28, 2003;
revised manuscript received July 14, 2003,
accepted July 21, 2003.
* Reprint requests and correspondence: Dr. Bradley H. Strauss, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, Canada M5BIW8.
straussb{at}smh.toronto.on.ca
OBJECTIVES: The role of atrial myocytes and extracellular matrix (ECM) changes in atrial chamber remodeling was studied in a canine model of heart failure (HF).
BACKGROUND: Cardiac remodeling is a key process mediating the progression of HF. Studies of the structural mechanisms of cardiac remodeling have been limited to the left ventricle. The structural alterations associated with atrial chamber remodeling in evolving HF have not been studied.
METHODS: Age- and weight-matched dogs were subjected to right ventricular pacing (240 beats/min) for one and three weeks to produce early and severe HF, respectively. Atrial tissues were assessed for myocyte and ECM changes.
RESULTS: Right atrial and left atrial (LA) pressures were significantly increased in early and severe HF. The LA wall tension index was significantly increased at both HF stages by 116% and 443%, respectively. Atrial collagen synthesis and degradation were significantly increased in severe HF. Gelatinase activity was significantly increased at both early and severe stages of HF. Gelatin zymography showed increased matrix metalloproteinases (MMP)-9 with early HF and increased MMP-2 with severe HF. The LA wall tension index was significantly correlated with gelatinase activity and collagen synthesis. Although total atrial collagen content was not changed, disarray of collagen fibers was observed. Atrial myocyte hypertrophy without evidence of apoptosis was also present in severe HF.
CONCLUSIONS: There is marked atrial chamber remodeling in canine pacing-induced HF, which is characterized by myocyte hypertrophy and dynamic collagen turnover. Atrial remodeling may contribute to the development of atrial arrhythmias and pulmonary hypertension and could offer a novel therapeutic target.
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Abbreviations and Acronyms
| | ACE | = angiotensin converting enzyme | | ECM | = extracellular matrix | | HF | = heart failure | | hpf | = high power field | | LA | = left atrial/atrium | | LV | = left ventricle/ventricular | | MMP | = matrix metalloproteinases | | mRNA | = messenger RNA | | TIMP | = tissue inhibitor of metalloproteinases | | RA | = right atrial/atrium | | TUNEL | = terminal deoxy nucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling |
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