Document Detail


Adenylate-cyclase VI transforms ventricular cardiomyocytes into biological pacemaker cells.
MedLine Citation:
PMID:  20067385     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: When sinus node or atrioventricular (AV) node cells are damaged by disease, the implantation of an artificial cardiac pacemaker becomes necessary. In search for a biological alternative, the objective of this study was to demonstrate whether in vivo adenoviral gene transfer of Adenylate-Cyclase type VI (AC-VI) can create biological pacemaker activity in a porcine AV node block model. Genetic therapy of arrhythmic disorders of the heart has been subject of extensive studies. Cyclic AMP is generated in response to Beta-adrenergic receptor stimulation and also binds to HCN channels, where it regulates spontaneous rhythmic activity in the sinus node.
MATERIALS AND METHODS: Adenoviruses encoding either AC-VI or Beta-Galactosidase (lacZ) gene were injected into the lateral wall of the left ventricle of adult pigs via anterolateral thoracotomy at a dose of 10(10) virus particles each. After 12 days, the AV node was ablated and three-dimensional electrophysiological cardiac mapping was performed using the Ensite electro-anatomical system.
RESULTS: After rapid ventricular pacing and administration of Isoprenalin, all animals of the AC-VI group exhibited an escape rhythm originating from the area of the left ventricular injection site at a rate of 100 + 7 beats/min (n = 5), whereas the escape rhythms in the control group (n = 4) originated from the right ventricle. Western blot analysis of the injection sites revealed significantly higher expression of AC-VI in the respective group as compared with the control group.
CONCLUSIONS: Our study demonstrates that AC-VI gene transfer has the potential to create a biological pacemaker system.
Authors:
Arjang Ruhparwar; Klaus Kallenbach; Gunnar Klein; Christoph Bara; Ali Ghodsizad; Daniel C Sigg; Matthias Karck; Axel Haverich; Michael Niehaus
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Tissue engineering. Part A     Volume:  16     ISSN:  1937-335X     ISO Abbreviation:  Tissue Eng Part A     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-31     Completed Date:  2010-08-26     Revised Date:  2011-10-20    
Medline Journal Info:
Nlm Unique ID:  101466659     Medline TA:  Tissue Eng Part A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1867-72     Citation Subset:  IM    
Affiliation:
Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany. arjang.ruhparwar@med.uni-heidelberg.de
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Adenylate Cyclase / genetics,  metabolism*
Animals
Biological Clocks / genetics,  physiology*
Blotting, Western
Electrophysiology
Heart Ventricles / cytology*
Humans
Myocytes, Cardiac / cytology*,  metabolism*
Swine
beta-Galactosidase / genetics,  metabolism
Chemical
Reg. No./Substance:
EC 3.2.1.23/beta-Galactosidase; EC 4.6.1.1/Adenylate Cyclase; EC 4.6.1.1/adenylyl cyclase 6

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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