This Article 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 Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Morawietz, H. Articles by Holtz, J. Search for Related Content PubMed PubMed Citation Articles by Morawietz, H. Articles by Holtz, J. Related Collections Congestive ACE/Angiotension receptors Physiological and pathological control of gene expression CV surgery: transplantation, ventricular assistance, cardiomyopathy

(Circulation. 2000;102:III-188.)
© 2000 American Heart Association, Inc.

Thoracic Transplantation and Ventricular Assist Devices

Deloading of the Left Ventricle by Ventricular Assist Device Normalizes Increased Expression of Endothelin ET_A Receptors But Not Endothelin-Converting Enzyme-1 in Patients With End-Stage Heart Failure

Henning Morawietz, PhD; Marten Szibor, MD; Winfried Goettsch, MS; Babett Bartling, MS; Matthias Barton, MD; Sidney Shaw, PhD; Reiner Koerfer, MD; Hans-Reinhard Zerkowski, MD; Juergen Holtz, MD

From the Institute of Pathophysiology (H.M., M.S., W.G., J.H.) and the Clinic for Cardiothoracic Surgery (B.B., H.-R.Z.), Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany; the Division of Cardiology (M.B.), Department of Medicine, University Hospital Zürich, Switzerland; the Department of Clinical Research (S.S.), University of Bern, Switzerland; the Department of Thoracic and Cardiovascular Surgery (R.K.), Heart Center North Rhine-Westphalia, Ruhr University of Bochum, Bad Oeynhausen, Germany; and the Division of Cardiothoracic Surgery (H.-R.Z.), University of Basel, Kantonspital, Basel, Switzerland.

Correspondence to Henning Morawietz, PhD, Institute of Pathophysiology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Magdeburger Str 18, D-06097 Halle, Germany. E-mail henning.morawietz{at}medizin.uni-halle.de

Background—Ventricular assist devices (VAD) are implanted in patients with end-stage heart failure for bridging the time until heart transplantation, resulting in hemodynamic unloading of the failing heart, improved cardiac contractile and mitochondrial function, and reversal of cardiac hypertrophy. It is unknown whether VAD unloading may affect the cardiac endothelin (ET) system, which has been proposed as one of the putative pathomechanisms of heart failure.

Methods and Results—With the use of standard-calibrated, competitive reverse-transcription–polymerase chain reaction mRNA expression of components of the ET system was analyzed in left ventricular myocardium from nonfailing donor hearts, from failing hearts without and with ACE inhibitor therapy, and from patients with end-stage heart failure at the time of VAD implantation and 103±15 days after VAD implantation during removal with subsequent heart transplantation. ET receptor A (ET_A) was markedly upregulated in failing human myocardium. This increased ET_A expression was not affected by ACE inhibitor treatment but was normalized by VAD unloading. ET_A expression before or after VAD implantation did not correlate with duration of VAD implantation or suppression of Pro-ANP mRNA. ET_B mRNA expression was unaffected by heart failure or VAD. In contrast, increased ET-converting enzyme-1 mRNA and ET-1 peptide levels in failing myocardium were partially normalized by ACE inhibition but not by VAD unloading.

Conclusions—We conclude that VAD implantation normalizes ET_A expression in failing human left ventricular myocardium, probably as the result of the beneficial effects of VAD unloading.

Key Words: endothelin • heart failure • heart-assist device