| The subtype-specific effects of droperidol on action potential duration in cellular and computational models of long QT syndrome. | |
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MedLine Citation:
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PMID: 20601449 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Droperidol is a highly potent butyrophenone used for the therapy of postoperative nausea and vomiting. Its cardiac safety in cardiovascular-healthy patients and those with long QT (LQT) syndrome is a matter of debate. In this study, we investigated whether droperidol has subtype-specific effects in cellular and computational models of LQT syndrome. METHODS: Left ventricular cardiac myocytes were isolated from adult guinea pig hearts. LQT1-like behavior was pharmacologically induced by chromanol 293B (10 micromol/L) and LQT2-like states by E4031 (10 micromol/L). Computational analysis was performed using the Luo-Rudy dynamic model. Data are given as mean + or - SEM. RESULTS: In control myocytes, droperidol lengthened action potentials in a concentration-dependent manner with a maximal prolongation of 37% + or - 13% (n = 4) at a concentration of 0.6 micromol/L. In LQT1-like myocytes, droperidol (0.6 micromol/L) further prolonged action potentials by 31% + or - 6% (n = 6) but shortened action potentials of LQT2-like myocytes by 11% + or - 2% (n = 8). Computational modeling supported the concept that droperidol, in addition to the rapid component of the delayed K(+) current, blocks depolarizing targets, such as the L-type Ca(2+) current, the Na(+)-Ca(2+) exchanger, and the Na(+)-K(+) adenosine triphosphatase. CONCLUSIONS: Droperidol has more detrimental effects on cardiac repolarization of LQT1-like than of LQT2-like myocytes suggesting subtype-specific cardiotoxic effects in patients with LQT syndrome. The subtype specificity of droperidol seems to be caused by a complex interaction of droperidol with several different molecular targets. This interaction deserves further investigation to establish the feasibility of a subtype-directed approach in the perioperative management of patients with LQT syndrome. |
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Authors:
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Alexander P Schwoerer; Julia Kebernik; Heimo Ehmke; Patrick Friederich |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-02 |
Journal Detail:
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Title: Anesthesia and analgesia Volume: 111 ISSN: 1526-7598 ISO Abbreviation: Anesth. Analg. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-24 Completed Date: 2010-09-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1310650 Medline TA: Anesth Analg Country: United States |
Other Details:
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Languages: eng Pagination: 638-46 Citation Subset: AIM; IM |
Affiliation:
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Department of Vegetative Physiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. schwoerer@uke.de |
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| MeSH Terms | |
Descriptor/Qualifier:
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Action Potentials
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drug effects* Adult Animals Anti-Arrhythmia Agents Antiemetics / pharmacology* Cardioplegic Solutions Cell Separation Chromans Computer Simulation Data Interpretation, Statistical Droperidol / pharmacology* Guinea Pigs Humans Long QT Syndrome / chemically induced, pathology* Models, Statistical Myocytes, Cardiac / drug effects Patch-Clamp Techniques Piperidines Potassium Channel Blockers Pyridines Sulfonamides |
| Chemical | |
Reg. No./Substance:
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0/Anti-Arrhythmia Agents; 0/Antiemetics; 0/Cardioplegic Solutions; 0/Chromans; 0/Piperidines; 0/Potassium Channel Blockers; 0/Pyridines; 0/Sulfonamides; 113558-89-7/E 4031; 163163-23-3/6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane; 548-73-2/Droperidol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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