• Tuberculosis and Respiratory Diseases
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• 제69권6호
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• pp.474-479
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• 2010

Torsades de pointes associated with a prolonged QT interval is a life-threatening arrhythmia, which may be induced by any of the following: drugs, electrolyte imbalances, severe bradycardia and intracranial hemorrhage. Torsades de pointes is characterized by beat-to-beat variations in the QRS complexes in any ECG leads with rates of 200~250 per minute. Fluoroquinolones are widely used and well tolerated antibacterial agents. However, prolongation of the QT interval leads rarely to Torsades de pointes as a significant adverse effect. So, it should be used with caution in high-risk patients for developing Torsades de pointes. We report one case of 67-year old man with contact burns who experienced Torsades de pointes, which probably resulted from the use of levofloxacin, and no further episode occurred after its withdrawal.

• 한국응급구조학회지
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• 제24권3호
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• pp.155-160
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• 2020

Torsades de pointes refers to polymorphic ventricular tachycardia (PMVT), which is caused by the suppression of potassium channels owing to genetic and electrolytic abnormalities, resulting in the extension of the QT interval. Symptoms range from spontaneous circulation recovery to fainting and sudden death. Defibrillation, magnesium correction, and the use of lidocaine as an antiarrhythmic agent are recommended as treatments for persistent torsades de pointes. Currently, only amiodarone is available in the ambulance; however, torsades de pointes does not respond efficiently to amiodarone because it suppresses potassium channels and increases the refractory period of the myocardium. Lidocaine, in contrast, reduces the relative refractory period of the myocardium caused by suppressing sodium channels; thus, it inhibits the occurrence of and treats arrhythmia. In cases where PMVT did not respond to defibrillation, the administration of lidocaine showed no difference in survival and discharge rates compared to amiodarone. Thus, ambulances must be equipped with provisions to administer lidocaine.

• Journal of Dental Anesthesia and Pain Medicine
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• 제20권3호
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• pp.165-171
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• 2020

The congenital long QT syndrome (LQTS) is an inherited cardiac disorder characterized by increased QT intervals and a tendency to experience ventricular tachycardia, which can cause fainting, heart failure, or sudden death. A 4-year-old female patient undergoing velopharyngeal correction surgery under general anesthesia suddenly developed Torsades de pointes. Although the patient spontaneously resolved to sinus rhythm without treatment, subsequent QT prolongation persisted. Here, we report a case of concealed LQTS with a literature review.

• The Korean Journal of Pain
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• 제31권1호
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• pp.3-9
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• 2018

Long QT syndrome is a cardiac repolarization disorder and is associated with an increased risk of torsades de pointes. The acquired form is most often attributable to administration of specific medications and/or electrolyte imbalance. This review provides insights into the risk for QT prolongation associated with drugs frequently used in the treatment of chronic pain. In the field of pain medicine all the major drug classes (i.e. NSAIDs, opioids, anticonvulsive and antidepressant drugs, cannabinoids, muscle relaxants) contain agents that increase the risk of QT prolongation. Other substances, not used in the treatment of pain, such as proton pump inhibitors, antiemetics, and diuretics are also associated with long QT syndrome. When the possible benefits of therapy outweigh the associated risks, slow dose titration and electrocardiography monitoring are recommended.

• The Korean Journal of Physiology and Pharmacology
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• 제27권3호
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• pp.267-275
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• 2023

Cardiotoxicity, particularly drug-induced Torsades de Pointes (TdP), is a concern in drug safety assessment. The recent establishment of human induced pluripotent stem cell-derived cardiomyocytes (human iPSC-CMs) has become an attractive human-based platform for predicting cardiotoxicity. Moreover, electrophysiological assessment of multiple cardiac ion channel blocks is emerging as an important parameter to recapitulate proarrhythmic cardiotoxicity. Therefore, we aimed to establish a novel in vitro multiple cardiac ion channel screening-based method using human iPSC-CMs to predict the drug-induced arrhythmogenic risk. To explain the cellular mechanisms underlying the cardiotoxicity of three representative TdP high- (sotalol), intermediate- (chlorpromazine), and low-risk (mexiletine) drugs, and their effects on the cardiac action potential (AP) waveform and voltage-gated ion channels were explored using human iPSC-CMs. In a proof-of-principle experiment, we investigated the effects of cardioactive channel inhibitors on the electrophysiological profile of human iPSC-CMs before evaluating the cardiotoxicity of these drugs. In human iPSC-CMs, sotalol prolonged the AP duration and reduced the total amplitude (TA) via selective inhibition of I_Kr and I_Na currents, which are associated with an increased risk of ventricular tachycardia TdP. In contrast, chlorpromazine did not affect the TA; however, it slightly increased AP duration via balanced inhibition of I_Kr and I_Ca currents. Moreover, mexiletine did not affect the TA, yet slightly reduced the AP duration via dominant inhibition of I_Ca currents, which are associated with a decreased risk of ventricular tachycardia TdP. Based on these results, we suggest that human iPSC-CMs can be extended to other preclinical protocols and can supplement drug safety assessments.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1999년도 학술발표회 진행표 및 논문초록
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• pp.64-64
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• 1999

Amitriptyline has been known to induce QT prolongation and ventricular arrhythmias such as torsades de pointes which causes sudden death. We studied the effects of amitriptyline on the human ether-a-go-go-related gene (HERG) channel expressed in Xenopus oocytes.(omitted)

• International Journal of Oral Biology
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• 제43권1호
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• pp.43-51
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• 2018

$K^+$ channels are key components of the primary and secondary basolateral $Cl^-$ pump systems, which are important for secretion from the salivary glands. Paroxetine is a selective serotonin reuptake inhibitor (SSRI) for psychiatric disorders that can induce QT prolongation, which may lead to torsades de pointes. We studied the effects of paroxetine on a human $K^+$ channel, human ether-a-go-go-related gene (hERG), expressed in Xenopus oocytes and on action potential in guinea pig ventricular myocytes. The hERG encodes the pore-forming subunits of the rapidly-activating delayed rectifier $K^+$ channel ($I_{Kr}$) in the heart. Mutations in hERG reduce $I_{Kr}$ and cause type 2 long QT syndrome (LQT2), a disorder that predisposes individuals to life-threatening arrhythmias. Paroxetine induced concentration-dependent decreases in the current amplitude at the end of the voltage steps and hERG tail currents. The inhibition was concentration-dependent and time-dependent, but voltage-independent during each voltage pulse. In guinea pig ventricular myocytes held at $36^{\circ}C$, treatment with $0.4{\mu}M$ paroxetine for 5 min decreased the action potential duration at 90% of repolarization ($APD_{90}$) by 4.3%. Our results suggest that paroxetine is a blocker of the hERG channels, providing a molecular mechanism for the arrhythmogenic side effects of clinical administration of paroxetine.

• 대한의용생체공학회:의공학회지
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• 제43권5호
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• pp.331-340
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• 2022

Early afterdepolarization (EAD), a significant cause of fatal ventricular arrhythmias including Torsade de Pointes (TdP) in long QT syndromes, is a depolarizing afterpotential at the plateau or repolarization phase in action potential (AP) profile early before completing one pace. AP duration prolongation is related to EAD but is not necessarily accounted for EAD. Several computational studies suggested EAD can form from an abnormality in the late plateau and/or repolarization phase of AP shape. In this sense, we hypothesized the slope during repolarization has the characteristics to predict TdP risk, mainly focusing on the maximum slope during repolarization (dVm/dt_{max_repol}). This study aimed to predict the sensitivity of dVm/dt_{max_repol} to ion channel conductances as a TdP risk metric through a population simulation considering multiple effects of simultaneous reduction in six ion channel conductances of g_NaL, g_Kr, g_Ks, g_to, g_K1, and g_CaL. Additionally, we verified the availability of dVm/dt_{max_repol} for TdP risk prediction through the correlation analysis with qNet, the representative TdP metric. We performed the population simulations based on the methodology of Gemmel et al. using the human ventricular myocyte model of Dutta et al. Among the sixion channel conductances, dVm/dt_{max_repol} and qNet responded most sensitively to the change in g_Kr, followed by g_NaL. Furthermore, dVm/dt_{max_repol} showed a statistically significant high negative correlation with qNet. The dVm/dt_{max_repol} values were significantly different according to three TdP risk levels of high, intermediate, and low by qNet (p<0.001). In conclusion, we suggested dVm/dt_{max_repol} as a new biomarker metric for TdP risk assessment.

• The Korean Journal of Pain
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• 제13권1호
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• pp.115-118
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• 2000

Stellate ganglion block is most commonly used in pain clinic because it is an easy procedure and it has broad indications reported that Angina pectoris, tachyarrhythmia and long QT syndrome (LQTS) are indicated. LQTS is a disorder of the abnormalities of cardiac sympathetic innervation and of myocardial repolarization. LQTS is characterized by marked prolongation of the QT interval, often manifestating as syncope, seizures, or sudden death due to polymorphic ventricular tachyarrhythmia known as torsades de pointes. Treatment of symptomatic patients usually begin with beta blocker. The elective treatment of LQTS patients unresponsive to beta blocker is the left cardiac sympathetic denervation. We report a case of LQTS patient who had received stellate ganglion block.

• 대한임상독성학회지
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• 제18권2호
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• pp.66-77
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• 2020

Purpose: The aims of the present study were twofold. First, the research investigated the effect of an individual's risk factors and the prevalence of psychotropic drugs on QTc prolongation, TdP (torsades de pointes), and death. Second, the study compared the risk scoring systems (the Mayo Pro-QT risk score and the Tisadale risk score) on QTc prolongation. Methods: The medical records of intoxicated patients who visited the emergency department between March 2010 and February 2019 were reviewed retrospectively. Among 733 patients, the present study included 426 psychotropic drug-intoxicated patients. The patients were categorized according to the QTc value. The known risk factors of QTc prolongation were examined, and the Mayo Pro-QT risk score and the Tisadale risk score were calculated. The analysis was performed using multiple logistic regression, Spearman correlation, and ROC (receiver operating characteristic). Results: The numbers in the mild to moderate group (male: 470≤QTc<500 ms, female: 480≤QTc<500 ms) and severe group (QTc≥500 ms or increase of QTc at least 60ms from baseline, both sex) were 68 and 95, respectively. TdP did not occur, and the only cause of death was aspiration pneumonia. The statically significant risk factors were multidrug intoxications of TCA (tricyclic antidepressant), atypical antipsychotics, an atypical antidepressant, panic disorder, and hypokalemia. The Tisadale risk score was larger than the Mayo Pro-QT risk score. Conclusion: Multiple psychotropic drugs intoxication (TCA, an atypical antidepressant, and atypical antipsychotics), panic disorder, and hypokalemia have been proven to be the main risk factors of QTc prolongation, which require enhanced attention. The present study showed that the Tisadale score had a stronger correlation and predictive accuracy for QTc prolongation than the Mayo Pro-QT score. As a result, the Tisadale risk score is a crucial assessment tool for psychotropic drug-intoxicated patients in a clinical setting.