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(Circulation. 1999;100:II-216.)
© 1999 American Heart Association, Inc.

Thoracic Transplantation and Ventricular Assist Devices

Myocardial Gene Expression of Regulators of Myocyte Apoptosis and Myocyte Calcium Homeostasis During Hemodynamic Unloading by Ventricular Assist Devices in Patients With End-Stage Heart Failure

Babett Bartling, MS; Hendrik Milting, PhD; Heike Schumann, MS; Dorothea Darmer, PhD; Lativ Arusoglu, MD; Michael Matthias Koerner, MD; Aly El-Banayosy, MD; Reiner Koerfer, MD; Juergen Holtz, MD; Hans-Reinhard Zerkowski, MD

From the Institute of Pathophysiology (B.B., H.S., D.D., J.H.) and the Clinic for Cardiothoracic Surgery (H.M., H.-R.Z.), Martin Luther University Halle-Wittenberg, Halle/Saale, Germany; the Department of Thoracic and Cardiovascular Surgery (L.A., M.M.K., A.E.-B., R.K.), Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Bad Oeynhausen, Germany; and the Clinic for Cardio-Thoracic Surgery (H.-R.Z.), University of Basel, Kantonspital, Basel, Switzerland.

Correspondence to Babett Bartling, Institut für Pathophysiologie, Martin-Luther-Universität Halle-Wittenberg, Magdeburger Str 18, D-06097 Halle/Saale, Germany. E-mail babett.bartling{at}medizin.uni-halle.de

Background—In patients with end-stage heart failure, characterized by an increased susceptibility to cardiomyocyte apoptosis and a labile cardiomyocyte calcium homeostasis, a ventricular assist device (VAD) is implanted for bridging to cardiac transplantation and results in myocardial unloading. Although phenotype changes in the failing heart are assumed to result from hemodynamic overload, the reversibility of these changes under unloading is unknown.

Methods and Results—By use of quantitative reverse-transcription polymerase chain reaction, mRNA expression analyses were performed on left ventricular specimens obtained from 10 nonfailing donor hearts (from 8 patients with dilated cardiomyopathy and 2 patients with coronary heart disease) at the time of VAD implantation and 36 to 169 days later during VAD removal with subsequent cardiac transplantation. In terminally failing hearts before VAD support, left ventricular mRNA analyses revealed increased Pro-ANP, reduced antiapoptotic Bcl-x_L and antiapoptotic Fas isoform FasExo6Del, and a decreased ratio of sarcoplasmic reticulum Ca²⁺-ATPase per sarcolemmal Na⁺-Ca²⁺ exchanger in comparison with nonfailing ventricles. After VAD unloading, ventricular transcription of Pro-ANP was immediately normalized, and apoptotic DNA fragmentation was attenuated. In patients with dilated cardiomyopathy, mRNAs of Bcl-x_L and FasExo6Del/Fas were enhanced depending on time on VAD. The Bcl-x_L mRNA level correlated positively with that of the Bcl-x_L protein. Transcription of sarcoplasmic reticulum Ca²⁺-ATPase/Na⁺-Ca²⁺ exchanger demonstrated recovery in only 4 of 10 patients.

Conclusions—Mechanical support of the failing heart induces a time-dependent change in myocardial gene expression compatible with a decreased susceptibility to apoptosis.

Key Words: apoptosis • calcium • heart failure • heart-assist device