HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Khan, A. Articles by Strauss, B. H. Search for Related Content PubMed PubMed Citation Articles by Khan, A. Articles by Strauss, B. H.

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.

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

This article has been cited by other articles:

				G. Laurent, G. Moe, X. Hu, H. Leong-Poi, K. A. Connelly, P. P.-S. So, A. Ramadeen, L. Doumanovskaia, A. Konig, J. Trogadis, et al. Experimental studies of atrial fibrillation: a comparison of two pacing models Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1206 - H1215. [Abstract] [Full Text] [PDF]

				G. Casaclang-Verzosa, B. J. Gersh, and T. S.M. Tsang Structural and functional remodeling of the left atrium: clinical and therapeutic implications for atrial fibrillation. J. Am. Coll. Cardiol., January 1, 2008; 51(1): 1 - 11. [Abstract] [Full Text] [PDF]

				F. Onorati, A. Esposito, G. Messina, A. di Virgilio, and A. Renzulli Right Isthmus Ablation Reduces Supraventricular Arrhythmias After Surgery for Chronic Atrial Fibrillation Ann. Thorac. Surg., January 1, 2008; 85(1): 39 - 48. [Abstract] [Full Text] [PDF]

				G. Laurent, G. Moe, X. Hu, B. Holub, H. Leong-Poi, J. Trogadis, K. Connelly, D. Courtman, B. H. Strauss, and P. Dorian Long chain n-3 polyunsaturated fatty acids reduce atrial vulnerability in a novel canine pacing model Cardiovasc Res, January 1, 2008; 77(1): 89 - 97. [Abstract] [Full Text] [PDF]

				F. Onorati, M. Bilotta, F. Borrello, M. Vatrano, A. di Virgilio, M. C. Comi, F. Perticone, and A. Renzulli Successful radiofrequency ablation determines atrio-ventricular remodelling and improves systo-diastolic function at tissue Doppler-imaging Eur. J. Cardiothorac. Surg., March 1, 2007; 31(3): 414 - 422. [Abstract] [Full Text] [PDF]

				M. Shah, F. G. Akar, and G. F. Tomaselli Molecular Basis of Arrhythmias Circulation, October 18, 2005; 112(16): 2517 - 2529. [Abstract] [Full Text] [PDF]

				W. Anne, R. Willems, T. Roskams, P. Sergeant, P. Herijgers, P. Holemans, H. Ector, and H. Heidbuchel Matrix metalloproteinases and atrial remodeling in patients with mitral valve disease and atrial fibrillation Cardiovasc Res, September 1, 2005; 67(4): 655 - 666. [Abstract] [Full Text] [PDF]

				Y Kamata, H Nara, H Sato, J-I Masuyama, S Minota, and T Yoshio Effect of steroid pulse therapy on mixed connective tissue disease with pulmonary arterial hypertension Ann Rheum Dis, August 1, 2005; 64(8): 1236 - 1237. [Full Text] [PDF]

				K. E. Porter, N. A. Turner, D. J. O'Regan, and S. G. Ball Tumor necrosis factor {alpha} induces human atrial myofibroblast proliferation, invasion and MMP-9 secretion: inhibition by simvastatin Cardiovasc Res, December 1, 2004; 64(3): 507 - 515. [Abstract] [Full Text] [PDF]