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Characterization of cardiac repolarization in the Göttingen minipig.
MedLine Citation:
PMID:  20951813     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
INTRODUCTION: The minipig represents an attractive experimental animal within cardiovascular research due to its extensive similarities to the human heart in terms of anatomy and physiology. Although minipigs have been used for cardiovascular research for decades no thorough characterization of the minipig cardiac electrophysiology has been performed. Therefore, we have for the first time characterized the minipig cardiac repolarization in a series of experiments ranging from mRNA quantification to in vivo studies.
METHODS: Göttingen minipigs were used throughout the study. Cardiac mRNA quantification was performed using quantitative PCR methods. For ex vivo experiments, hearts were excised using cardioplegic procedures and Langendorff and microelectrode action potential recordings were performed. Effects of temperature in vivo were recorded in anesthetized animals.
RESULTS: On the mRNA level the expression profile of major cardiac ion channel proteins in both atria and ventricle was very similar to what has been reported for humans. In both intact isolated heart and isolated endocardial strips the I(Kr) blocker dofetilide increased action potential duration (APD). The I(Ks) blocker HMR1556 increased APD and triangulation only when I(Kr) was blocked with dofetilide. In the presence of I(Kr) and I(Ks) blockade a reduction of [K(+)](e) resulted in a marked increase in APD(90) in isolated hearts. I(K1) blockade with Ba(2+) increased APD in whole heart and isolated endocardium. In isolated endocardium, β-adrenergic stimulation with isoprenaline resulted in an increase in APD and potential amplitude but a decrease in triangulation. There was a rate-dependent decrease in APD in both whole heart and isolated endocardium. In vivo and ex vivo investigations revealed a negative correlation between temperature and duration of cardiac repolarization.
DISCUSSION: Our results point toward the minipig being a promising species for cardiac safety research.
Authors:
Morten Laursen; Søren-Peter Olesen; Morten Grunnet; Tomas Mow; Thomas Jespersen
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Publication Detail:
Type:  Journal Article     Date:  2010-10-15
Journal Detail:
Title:  Journal of pharmacological and toxicological methods     Volume:  63     ISSN:  1873-488X     ISO Abbreviation:  J Pharmacol Toxicol Methods     Publication Date:    2011 Mar-Apr
Date Detail:
Created Date:  2011-02-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9206091     Medline TA:  J Pharmacol Toxicol Methods     Country:  United States    
Other Details:
Languages:  eng     Pagination:  186-95     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
H. Lundbeck A/S, Ottiliavej 9, 2500 Valby, Copenhagen, Denmark; The Danish National Research Foundation Centre for Cardiac Arrhythmia, Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 2, 2200 Copenhagen N, Denmark.
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