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(Circulation. 2005;112:I-46 – I-50.)
© 2005 American Heart Association, Inc.

Cardiac Transplantation and Surgery for Congestive Heart Failure

Myocardial Insulin-Like Growth Factor-I Gene Expression During Recovery From Heart Failure After Combined Left Ventricular Assist Device and Clenbuterol Therapy

Paul J. R. Barton, PhD; Leanne E. Felkin, BSc; Emma J. Birks, MRCP, PhD; Martin E. Cullen, PhD; Nicholas R. Banner, FRCP; Suzanne Grindle, BSc; Jennifer L. Hall, PhD; Leslie W. Miller, MD; Magdi H. Yacoub, FRS

From the National Heart and Lung Institute, Imperial College London, Heart Science Centre, London (P.J.R.B., L.E.F., M.E.C., M.H.Y.), and Royal Brompton and Harefield NHS Trust, Harefield, Middlesex (E.J.B., N.R.B.), UK; and Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis (S.G., J.L.H., L.W.M.).

Correspondence to Paul J.R. Barton, Molecular Biology, Heart Science Centre, Harefield, Middlesex UB9 6JH, UK. E-mail p.barton{at}imperial.ac.uk

Background— Patients who undergo mechanical support with a left ventricular assist device (LVAD) exhibit reverse remodeling and in some cases recover from heart failure. We have developed a combination therapy using LVAD support combined with pharmacological therapy to maximize reverse remodeling, followed by the ß₂ adrenergic agonist clenbuterol. We recently found that clenbuterol induces insulin-like growth factor I (IGF-I) in cardiac myocytes in vitro. The purpose of this study is to examine IGF-I expression in recovery patients after combination therapy.

Methods and Results— Myocardial mRNA levels were determined by real-time quantitative polymerase chain reaction in 12 recovery patients (at LVAD implantation, explantation, and 1 year after explantation). IGF-I mRNA was elevated at the time of LVAD explantation relative to donors, with 2 groups distinguishable: Those with low IGF-I mRNA at implantation who showed significant increase during recovery and those with high IGF-I mRNA at implantation who remained high. Levels returned to normal by 1 year after explantation. Microarray analysis of implantation and explantation samples of recovery patients further revealed elevated IGF-II and IGF binding proteins IGFBP4 and IGFBP6. IGF-I levels correlated with stromal cell-derived factor mRNA measured both in LVAD patients and in a wider cohort of heart failure patients.

Conclusions— The data suggest involvement of elevated myocardial IGF-I mRNA in recovery. IGF-I may act to limit atrophy and apoptosis during reverse remodeling and to promote repair and regeneration in concert with stromal cell derived factor.

Key Words: polymerase chain reaction • myocardium • heart failure • growth substances • ventricles