JTCS Tips for Better Browsing
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Walter H. Merrill
Shahab A. Akhter
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pandalai, P. K.
Right arrow Articles by Akhter, S. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pandalai, P. K.
Right arrow Articles by Akhter, S. A.
Related Collections
Right arrow Mechanical Circulatory Assistance
Right arrow Molecular biology

J Thorac Cardiovasc Surg 2006;131:975-980
© 2006 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Restoration of myocardial ß-adrenergic receptor signaling after left ventricular assist device support

Prakash K. Pandalai, MD, Christian F. Bulcao, MD, Walter H. Merrill, MD, Shahab A. Akhter, MD *

Department of Surgery, Section of Cardiothoracic Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Received for publication October 5, 2005; revisions received December 15, 2005; accepted for publication January 10, 2006.

* Address for reprints: Shahab A. Akhter, MD, Department of Surgery, Section of Cardiothoracic Surgery, University of Cincinnati College of Medicine, 231 Albert B. Sabin Way ML0558, Cincinnati, OH 45267-0558. (Email: shahab.akhter{at}uc.edu).

OBJECTIVE: Left ventricular assist device support for patients with chronic heart failure can significantly improve ß-adrenergic receptor signaling, which is likely critical to myocardial recovery. The mechanism underlying the restoration of ß-adrenergic receptor signaling is unclear. This study investigates our hypothesis that restoration of cardiac ß-adrenergic receptor signaling by left ventricular assist devices results from inhibition of the G protein–coupled receptor kinase-2, a G protein–coupled receptor kinase that specifically phosphorylates and desensitizes agonist-occupied ß-adrenergic receptors.

METHODS: Left ventricular ß-adrenergic receptor signaling was assessed in biopsy specimens taken from patients with chronic heart failure (n = 12) at the time of left ventricular assist device implantation (heart failure group) and again at the time of heart transplantation (left ventricular assist device group). Signaling was also studied in left ventricular biopsy specimens from nonfailing control (n = 8) hearts (nonfailing control group). Signaling was assessed by measuring sarcolemmal membrane ß-adrenergic receptor density, adenylyl cyclase activity, G protein expression, and G protein–coupled receptor kinase-2 expression and activity.

RESULTS: Left ventricular ß-adrenergic receptor signaling was severely decreased in the heart failure group versus that seen in the nonfailing control group, as demonstrated by adenylyl cyclase activity. G protein–coupled receptor kinase-2 expression and activity was increased 3-fold in the heart failure group versus that seen in the nonfailing control group. After left ventricular assist device support, ß-adrenergic receptor signaling was restored to levels similar to those seen in the nonfailing control group. G protein–coupled receptor kinase-2 expression and activity were markedly diminished after left ventricular assist device support compared with that seen in the heart failure group and were not different from that seen in the nonfailing control group.

CONCLUSION: In chronic heart failure left ventricular assist device support leads to restoration of cardiac ß-adrenergic receptor signaling. The primary mechanism appears to be diminished myocardial G protein–coupled receptor kinase-2 activity. This demonstrates the potentially beneficial effects of G protein–coupled receptor kinase-2 inhibition on ß-adrenergic receptor signaling in heart failure and might represent a novel therapeutic strategy for this disease process.

Abbreviations and Acronyms AC = adenylyl cyclase; ANOVA = analysis of variance; ATP = adenosine triphosphate; ßAR = ß-adrenergic receptor; ßARK1 = ß-adrenergic receptor kinase-1; Bmax = total ßAR density; cAMP = cyclic adenosine monophosphate; DU = densitometry units; GRK = G protein–coupled receptor kinase; HF = heart failure; LVAD = left ventricular assist device; NF group = nonfailing group






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS
Copyright © 2006 by The American Association for Thoracic Surgery.