Key result
Droperidol prolonged action potentials by 31% in LQT1-like myocytes but shortened them by 11% in LQT2-like myocytes, suggesting subtype-specific cardiotoxic effects.
Why the study?
Does droperidol have subtype-specific effects on action potential duration in cellular and computational models of Long QT syndrome?
Does droperidol have subtype-specific effects on action potential duration in cellular and computational models of Long QT syndrome?
Droperidol exhibits subtype-specific effects on cardiac repolarization, worsening action potential prolongation in LQT1-like models while shortening it in LQT2-like models.
Should not yet change droperidol use in long QT syndrome; hypothesis-generating for subtype-specific repolarization effects.
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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Schwoerer et al. (2010) studied Long QT syndrome (cellular and computational models). Droperidol vs. Control myocytes was evaluated on Action potential duration. Droperidol prolonged action potentials by 31% in LQT1-like myocytes but shortened them by 11% in LQT2-like myocytes, suggesting subtype-specific cardiotoxic effects.
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