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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http://dx.doi.org/10.1213/ANE.0b013e3181e41996 | DOI Listing |
J Electrocardiol
November 2024
Department of Cardiology, Morriston Regional Cardiac Centre, Morriston Hospital, Heol Maes Eglwys, Swansea SA6 6NL, UK.
Biomolecules
November 2024
Cardiogenetic Center, Rare Diseases and Medical Genetics Units, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
Inherited cardiac channelopathies are major causes of sudden cardiac death (SCD) in young people. Genetic testing is focused on the identification of single-nucleotide variants (SNVs) by Next-Generation Sequencing (NGS). However, genetically elusive cases can carry copy number variants (CNVs), which need specific detection tools.
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December 2024
Centre for Cardiovascular Diseases, Henan Key Laboratory of Hereditary Cardiovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, China. Electronic address:
Calmodulin mutations can cause life-threatening long QT syndrome involving CALM1, CALM2, and CALM3. In this study, human induced pluripotent stem cells ZZUNEUi030-A were derived from a female patient with heterozygous CALM2 gene c. 395A → T by Sendai virus non-integrated reprogramming technology.
View Article and Find Full Text PDFUnlabelled: The cardiac KCNQ1+KCNE1 (I ) channel regulates heart rhythm in both normal and stress conditions. Under stress, the β-adrenergic stimulation elevates the intracellular cAMP level, leading to KCNQ1 phosphorylation by protein kinase A and increased I , which shortens action potentials to adapt to accelerated heart rate. An impaired response to the β-adrenergic stimulation due to KCNQ1 mutations is associated with the occurrence of a lethal congenital long QT syndrome (type 1, also known as LQT1).
View Article and Find Full Text PDFBiochem Biophys Res Commun
June 2024
Department of Biology, MSU-BIT University, Shenzhen, Guangdong Province, China; Department of Biology, Moscow Lomonosov University, Moscow, Russia. Electronic address:
Here, we characterized the p.Arg583His (R583H) Kv7.1 mutation, identified in two unrelated families suffered from LQT syndrome.
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