ABSTRACT
The slowly and rapidly activating delayed rectifier K+ channels (IKs and IKr, respectively) contribute to the repolarization of ventricular action potential in human heart and thereby determine QT interval on an electrocardiogram. Loss-of-function mutations in genes encoding IKs and IKr cause type 1 and type 2 long QT syndrome (LQT1 and LQT2, respectively), accompanied by a high risk of malignant ventricular arrhythmias and sudden cardiac death. This study was designed to investigate which cardiac electrophysiological conditions exaggerate QT-prolonging and arrhythmogenic effects of sevoflurane. We used the O'Hara-Rudy dynamic model to reconstruct human ventricular action potential and a pseudo-electrocardiogram, and simulated LQT1 and LQT2 phenotypes by decreasing conductances of IKs and IKr, respectively. Sevoflurane, but not propofol, prolonged ventricular action potential duration and QT interval in wild-type, LQT1 and LQT2 models. The QT-prolonging effect of sevoflurane was more profound in LQT2 than in wild-type and LQT1 models. The potent inhibitory effect of sevoflurane on IKs was primarily responsible for its QT-prolonging effect. In LQT2 model, IKs was considerably enhanced during excessive prolongation of ventricular action potential duration by reduction of IKr and relative contribution of IKs to ventricular repolarization was markedly elevated, which appears to underlie more pronounced QT-prolonging effect of sevoflurane in LQT2 model, compared with wild-type and LQT1 models. This simulation study clearly elucidates the electrophysiological basis underlying the difference in QT-prolonging effect of sevoflurane among wild-type, LQT1 and LQT2 models, and may provide important information for developing anesthetic strategies for patients with long QT syndrome in clinical settings.
Subject(s)
Action Potentials/drug effects , Heart Rate/drug effects , Heart Ventricles/drug effects , Long QT Syndrome/chemically induced , Models, Cardiovascular , Myocytes, Cardiac/drug effects , Romano-Ward Syndrome/chemically induced , Sevoflurane/toxicity , Case-Control Studies , Computer Simulation , Delayed Rectifier Potassium Channels/genetics , Delayed Rectifier Potassium Channels/metabolism , Heart Ventricles/metabolism , Heart Ventricles/physiopathology , Humans , Long QT Syndrome/genetics , Long QT Syndrome/metabolism , Long QT Syndrome/physiopathology , Myocytes, Cardiac/metabolism , Propofol/toxicity , Risk Assessment , Risk Factors , Romano-Ward Syndrome/genetics , Romano-Ward Syndrome/metabolism , Romano-Ward Syndrome/physiopathology , Time FactorsABSTRACT
The authors present an overview of the most often discussed questions concerning citalopram, i.e. its proven effect on the QT interval and related dose reductions. They discuss citalopram's antiplatelet effect including the most recent data and draw attention to serotonin syndrome as its incidence is still underestimated. They go on to discuss hyponatremia pointing out that this condition may develop even in those taking low doses of citalopram. Finally, the authors provide a brief overview of the latest findings on osteoporosis and the serotonergic mechanism inducing it in individuals treated with a selective serotonin reuptake inhibitor.
