Document Detail


The subtype-specific effects of droperidol on action potential duration in cellular and computational models of long QT syndrome.
MedLine Citation:
PMID:  20601449     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Alexander P Schwoerer; Julia Kebernik; Heimo Ehmke; Patrick Friederich
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-02
Journal Detail:
Title:  Anesthesia and analgesia     Volume:  111     ISSN:  1526-7598     ISO Abbreviation:  Anesth. Analg.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-24     Completed Date:  2010-09-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1310650     Medline TA:  Anesth Analg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  638-46     Citation Subset:  AIM; IM    
Affiliation:
Department of Vegetative Physiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. schwoerer@uke.de
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MeSH Terms
Descriptor/Qualifier:
Action Potentials / 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:
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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