• 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.

• Biomolecules & Therapeutics
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• 제17권1호
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• pp.1-11
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• 2009

Since the Committee for Proprietary Medicinal Products (CPMP) of the European Union issued in 1997 a "points to consider" document for the assessment of the potential for QT interval prolongation by non-cardiovascular agents to predict drug-induced torsades de pointes (TdP), the QT liability has become the critical safety issue in the development of pharmaceuticals. As TdP is usually linked to delayed cardiac repolarization, international guideline (ICH S7B) has advocated the standard repolarization assays such as in vitro IKr (hERG current) and in vivo QT interval, or in vitro APD (as a follow up) as the best biomarkers for predicting the TdP risk. However, the recent increasing evidence suggests that the currently used above biomarkers and/or assays are not fully predictive for TdP, but also does not address potential new druginduced TdP due to the selective disruption of hERG protein trafficking to the cell membrane or VT and/or VF with QT shortening. There is, therefore, an urgent need for other surrogate markers or assays that can predict the proarrhythmic potential of drug candidate. In this review, we provide an ideal pre-clinical strategy to predict the potentials of QT liability and lethal arrhythmia of the drug candidates with recent issues in this field in mind, not at the expense of discarding therapeutically innovative drugs.

• The Korean Journal of Physiology and Pharmacology
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• 제6권1호
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• pp.1-7
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• 2002

Congenital Long QT syndrome (LQTs) is a relatively rare pathologic disorder but results frequently in sudden cardiac death. Of the six LQTs that have been clinically described, five have been worked out for their genetic and biophysical profile. Most are generated by mutations which cause a loss of function in two delayed $K^+$ currents, $i_{Ks}\;and\;i_{Kr}.$ One syndrome is generated by mutations in the $Na^+$ channel which causes essentially a gain of function in the channel. Clinically the syndromes are characterized by slowed repolarization of the cardiac ventricular action potential and the occurrence of typical arrhythmias with undulating peaks in the electrocardiogram, called Torsade de Pointes. Arrhythmias are initiated by early or delayed afterdepolarizations and continue as reentry. Triggers for cardiac events are exercise (swimming; LQT1), emotion (arousal; LQT2) and rest/sleep (LQT3). ${\beta}-blockers$ have a high efficacy in the treatment of LQT1 and LQT2. In LQT3 their use is questionable. The study of congenital LQTsyndromes is a remarkable example of how basic and clinical science converge and take profit of each other's contribution.

• 대한의생명과학회지
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• 제16권4호
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• pp.299-305
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• 2010

KCNE1 is the causal gene of long QT syndrome. KCNE1 gene is located in chromosome 21. In compliance with this KCNE1 gene the proteins come out. KCNE1 is responsible for $K^+$ channel which maintains the normal function of the heart muscle for contraction. Affected individuals manifest prolongation of the QT interval on electrocardiongrams, a sign of abnormal cardiac repolarization. The clinical features of LQT result from episodic cardiac arrhythmias, such as torsade de pointes and ventricular fibrllation. Blood DNA was isolated and kept in $4^{\circ}C$ refrigerator. The KCNE1 gene was amplified by PCR method and about 414 bp band was identified by agarose gel electrophoresis. PCR products were inserted into pGEX-4T-1 vector in order to express KCNE1 protein after treatment with IPTG SDS-PAGE was carried out and the protein band which was about 47 kDa was clearly odserved. Results of this study would contribute to the detailed understanding of KCNE1 protein function and to designing better treatment of Long QT symdrome.

• Annals of Occupational and Environmental Medicine
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• 제34권
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• pp.16.1-16.11
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• 2022

Background: Antimony is used in catalysts, pesticides, brake systems, pharmaceuticals, and synthetic fire retardants in the plastic, paint, and rubber industries. Accumulation of trivalent antimony compounds in the body can cause cardiotoxic effects and increase the risk of electrocardiogram (ECG) abnormalities and sudden death. Antimony exposure can result in action potential prolongation, causing a cardiac repolarization delay, which appears as QTc prolongation and T-wave abnormalities on the ECG. There are no studies on antimony-associated cardiac toxicity in Korea. Case presentation: Accordingly, the present study reports cases of ECG abnormalities in workers handling antimony trisulfide at a company located in the Gyeongsangbuk-do region. Nineteen workers employed at an automobile brake lining manufacturer were exposed to antimony trisulfide dust through thermoforming, grinding, and drilling processes. In 2020, the workers were reported to work 12-hour shifts, 5 days a week. The time-weighted average (TWA) of antimony trisulfide exposure measured in workers was 0.0028 mg/m³. Two workers were excluded from the analysis due to pre-existing medical conditions (cardiovascular disease). Of the remaining 17 workers, ECG abnormalities were found in 41% (seven out of 17: four with QTc prolongation and T-wave abnormalities; two with only T-wave abnormalities; and one with only QTc prolongation). Conclusions: This case report outlines the first few cases in Korea in which potential cardiac toxicity caused by occupational exposure to antimony was identified. However, data regarding cardiac toxicity caused by antimony exposure are still lacking in Korea; thus, additional studies are needed to identify causal relationships.

• 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.

• Biomolecules & Therapeutics
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• 제18권4호
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• pp.448-453
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• 2010

Drug-induced long QT syndrome is known to be associated with the onset of torsades de pointes (TdP), resulting in a fatal ventricular arrhythmia. QT interval prolongation can result from blocking the human ether-a-go-go-related gene (hERG) channel, which is important for the repolarization of cardiac action potential. Nicardipine, a Ca-channel blocker and antihypertensive agent, has been reported to increase the risk of occasional serious ventricular arrhythmias. We studied the effects of nicardipine on hERG $K^+$ channels expressed in HEK293 cells and Xenopus oocytes. The cardiac electrophysiological effect of nicardipine was also investigated in this study. Our results revealed that nicardipine dose-dependently decreased the tail current of the hERG channel expressed in HEK293 cells with an $IC_{50}$ of 0.43 ${\mu}M$. On the other hand, nicardipine did not affect hERG channel trafficking. Taken together, nicardipine inhibits the hERG channel by the mechanism of short-term channel blocking. Two S6 domain mutations, Y652A and F656A, partially attenuated (Y652A) or abolished (F656A) the hERG current blockade, suggesting that nicardipine blocks the hERG channel at the pore of the channel.

• The Korean Journal of Physiology and Pharmacology
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• 제24권6호
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• pp.545-553
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• 2020

Aripiprazole is a quinolinone derivative approved as an atypical antipsychotic drug for the treatment of schizophrenia and bipolar disorder. It acts as with partial agonist activities at the dopamine D2 receptors. Although it is known to be relatively safe for patients with cardiac ailments, less is known about the effect of aripiprazole on voltage-gated ion channels such as transient A-type K⁺ channels, which are important for the repolarization of cardiac and neuronal action potentials. Here, we investigated the effects of aripiprazole on Kv1.4 currents expressed in HEK293 cells using a whole-cell patch-clamp technique. Aripiprazole blocked Kv1.4 channels in a concentration-dependent manner with an IC₅₀ value of 4.4 μM and a Hill coefficient of 2.5. Aripiprazole also accelerated the activation (time-to-peak) and inactivation kinetics. Aripiprazole induced a voltage-dependent (δ = 0.17) inhibition, which was use-dependent with successive pulses on Kv1.4 currents without altering the time course of recovery from inactivation. Dehydroaripiprazole, an active metabolite of aripiprazole, inhibited Kv1.4 with an IC₅₀ value of 6.3 μM (p < 0.05 compared with aripiprazole) with a Hill coefficient of 2.0. Furthermore, aripiprazole inhibited Kv4.3 currents to a similar extent in a concentration-dependent manner with an IC₅₀ value of 4.9 μM and a Hill coefficient of 2.3. Thus, our results indicate that aripiprazole blocked Kv1.4 by preferentially binding to the open state of the channels.

• 대한수의학회지
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• 제41권3호
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• pp.311-317
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• 2001

In this work we have investigated the physiological effects of $MgCl_2$ in isolated atrium, papillary muscle, perfused heart and anesthesized guinea pig, The addition or infusion of $MgCl_2$ (0~20 mM or mg/kg) to perfused hearts and to anesthesized guinea pigs induced a marked and dose-dependent negative chronotropic effect. The sinoatrial node automaticity could also be reduced by $MgCl_2$. The addition of $MgCl_2$to isolated atria and to papillary muscles induced a marked and dose-dependent negative inotropic effect. The threshold voltage could be increased by $MgCl_2$in papillary muscle. Increasing $MgCl_2$ shortened the action potential duration (APD) in dose-dependent manner at 30% ($APD_{30}$) and 90% repolarization ($APD_{90}$) measured with conventional microelectrode technique in papillary muscle. In anesthesized guinea pig, the magnesium infusion resulted in a dose-dependent drop in blood pressure. These results suggested that magnesium is closely associated with cardiac physiological condition and exerts antiarrhythmic activities.

• 생명과학회지
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• 제18권9호
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• pp.1278-1283
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• 2008

본 연구의 목적은 type 1 당뇨 아동에서 12주 유산소운동 트레이닝이 심장 QT 간격과 심혈관 위험 인자들에 어떠한 변화가 있는지를 조사하였다. 연구의 대상자는 9-17세 사이의 type 1 당뇨 아동 11명을 대상으로 하였다. 대상자들은 유산소운동 프로그램을 총 12주간 주 3회 실시하였다. 운동 강도는 3주까지 HRR 45%, 그 이후에는 HRR 55%를 적용하였다. 심장 QT 간격의 평가는 심박수 변이성 파워 스펙트랄 분석을 이용하였으며, 심혈관 위험인자들은 대상자들의 혈액 샘플을 채취하여 검사하였다. 연구결과 유산소운동 트레이닝 후 수축기 혈압(p<0.05)과 확장기 혈압(p<0.05)에서 유의한 감소가 있었다. 또한 심장 QT 간격(p<0.05), TC 농도(p<0.05), 그리고 HDL-C 농도(p<0.05)의 감소를 보였다. 이상의 연구결과와 선행연구를 고려할 때 운동 강도와 빈도가 고려된 장기간 규칙적인 신체활동은 type 1 당뇨 아동의 당뇨 합병증 예방 및 심혈관 건강관리에 효과적이고 중요한 작용을 할 수 있으리라 기대할 수 있다.