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(Circulation. 2002;106:I-23.)
© 2002 American Heart Association, Inc.

Surgery for Valvular Heart Disease

Left Ventricular Reverse Remodeling After Surgical Therapy for Aortic Stenosis: Correlation to Renin-Angiotensin System Gene Expression

Thomas Walther, MD, PhD; Andreas Schubert, PhD; Volkmar Falk, MD, PhD; Christian Binner, MD; Claudia Walther, MD; Nico Doll, MD; Alex Fabricius, MD; Stefan Dhein, MD, PhD; Jan Gummert, MD, PhD; Friedrich W. Mohr, MD, PhD

From the Universität Leipzig, Herzzentrum, Klinik für Herzchirurgie, Leipzig, Germany.

Correspondence to Dr. Thomas Walther, Universität Leipzig, Herzzentrum, Klinik für Herzchirurgie, Strümpellstr. 39, D-04289 Leipzig, Germany. E-mail walt{at}medizin.uni-leipzig.de

Background Surgical therapy for aortic stenosis leads to reverse remodeling, with normalization of left ventricular hypertrophy (LVH). The aim of this study was to examine Renin-Angiotensin system (RAS) gene expression in this setting.

Methods Growing sheep (n=44) underwent supracoronary aortic banding for controlled induction of LVH at the age of 6 to 8 months (A=baseline). Surgical revision to completely release the pressure gradient was performed 8.3±1 months later (B). The animals were sacrificed after another 10.1±2 months (C). Along with hemodynamic measurements, subtractive hybridization and competitive polymerase chain reaction were applied to quantify mRNA expression for angiotensin-converting enzyme (ACE) and angiotensin receptors 1 and 2 (AT₁-R and AT₂-R).

Results Left ventricular mass index was 82±21 g (A), 150±33 g (B), and 78±18 g (C), P<0.01. Left ventricular function and cardiac index remained stable. Myocardial fiber diameter was 11.3±0.8 (A), 15.9±1.2 (B), and 11.4±1 (C) µm, P<0.01. Gene expression was as follows: ACE 0.8±0.05 (A), 1.3±0.08 (B), and 0.9±0.06 (C), P<0.01; AT₁-R 0.7±0.06 (A), 0.9±0.07 (B), and 0.3±0.04 (C), P<0.01; AT₂-R 0.5±0.05 (A), 0.2±0.04 (B), and 0.5±0.05 (C), P<0.01.

Conclusion LVH in aortic stenosis coincides with significant alterations of the RAS. Surgical therapy leads to reverse remodeling, which is paralleled by regression of RAS gene expression.

Key Words: aortic stenosis • left ventricular hypertrophy • renin-angiotensin-system • gene expression