| Bupivacaine Destabilizes Action Potential Duration in Cellular and Computational Models of Long QT Syndrome 1. | |
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MedLine Citation:
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PMID: 22003215 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Background:The effects of the local anesthetic bupivacaine on cardiac action potentials (APs) are mainly attributed to inhibition of cardiac Na(+) channels. The relevance of its ability to also induce high-affinity blockade of human ether-à-gogo-related gene (hERG) channels is unclear. We investigated whether this interaction may functionally become more significant in cellular and computational models of long (L)QT syndromes.Methods:Left ventricular cardiomyocytes were isolated from adult guinea pig hearts, and bupivacaine-induced effects on APs were investigated using the patch-clamp technique. LQT-like states were pharmacologically induced by either blocking I(Ks) (LQT1-like, 10 μmol/L chromanol 293B), or I(Kr) (LQT2-like, 10 μmol/L E4031). Computational analysis of bupivacaine's effects was based on the Luo-Rudy dynamic model.Results:Bupivacaine induced dose-dependent AP shortening in control myocytes. However, in the presence of 1 to 30 μmol/L bupivacaine, a high variability in AP duration with AP prolongations of up to 40% was observed. This destabilizing effect on AP duration was significantly increased in LQT1-like but not in LQT2-like myocytes. Similarly, the incidence of AP prolongations in the presence of 3 μmol/L bupivacaine was significantly increased from 6% in control myocytes to 24% in LQT1-like but not in LQT2-like myocytes. Computational modeling supported the concept that this bupivacaine-induced AP instability and the AP prolongations in the control and LQT1-like myocytes were caused by inhibition of hERG channels.Conclusions:This study provides evidence that bupivacaine induces inhibition of hERG channels, which is functionally silent under normal conditions but will become more relevant in LQT1-like states in which repolarization relies to a larger degree on hERG channels. Interactions with ion channels other than cardiac Na(+) channels may, therefore, determine the net cardiac effects of bupivacaine when the normal balance of ionic currents is altered. |
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Authors:
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Alexander P Schwoerer; Roman Zenouzi; Heimo Ehmke; Patrick Friederich |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-14 |
Journal Detail:
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Title: Anesthesia and analgesia Volume: - ISSN: 1526-7598 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1310650 Medline TA: Anesth Analg Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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From the *Department of Cellular and Integrative Physiology, University Medical Center Hamburg-Eppendorf, Hamburg; and. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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