• Korean Circulation Journal
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• v.53 no.4
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• pp.239-250
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• 2023

Background and Objectives: Brugada syndrome (BrS) is an inherited arrhythmia syndrome that presents as sudden cardiac death (SCD) without structural heart disease. One of the mechanisms of SCD has been suggested to be related to the uneven dispersion of transient outward potassium current (I_to) channels between the epicardium and endocardium, thus inducing ventricular tachyarrhythmia. Artemisinin is widely used as an antimalarial drug. Its antiarrhythmic effect, which includes suppression of I_to channels, has been previously reported. We investigated the effect of artemisinin on the suppression of electrocardiographic manifestations in a canine experimental model of BrS. Methods: Transmural pseudo-electrocardiograms and epicardial/endocardial transmembrane action potentials (APs) were recorded from coronary-perfused canine right ventricular wedge preparations (n=8). To mimic the BrS phenotypes, acetylcholine (3 μM), calcium channel blocker verapamil (1 μM), and I_to agonist NS5806 (6-10 μM) were used. Artemisinin (100-150 μM) was then perfused to ameliorate the ventricular tachyarrhythmia in the BrS models. Results: The provocation agents induced prominent J waves in all the models on the pseudo-electrocardiograms. The epicardial AP dome was attenuated. Ventricular tachyarrhythmia was induced in six out of 8 preparations. Artemisinin suppressed ventricular tachyarrhythmia in all 6 of these preparations and recovered the AP dome of the right ventricular epicardium in all preparations (n=8). J wave areas and epicardial notch indexes were also significantly decreased after artemisinin perfusion. Conclusions: Our findings suggest that artemisinin has an antiarrhythmic effect on wedge preparation models of BrS. It might work by inhibition of potassium channels including I_to channels, subsequently suppressing ventricular tachycardia/ventricular fibrillation.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.597-605
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• 2018

In this study, we demonstrated the inhibitory effect of the Class Ic antiarrhythmic agent propafenone on voltage-dependent $K^+$ (Kv) channels using freshly isolated coronary artery smooth muscle cells from rabbits. The Kv current amplitude was progressively inhibited by propafenone in a dose-dependent manner, with an apparent $IC_{50}$ value of $5.04{\pm}1.05{\mu}M$ and a Hill coefficient of $0.78{\pm}0.06$. The application of propafenone had no significant effect on the steady-state activation and inactivation curves, indicating that propafenone did not affect the voltage-sensitivity of Kv channels. The application of train pulses at frequencies of 1 or 2 Hz progressively increased the propafenone-induced inhibition of the Kv current. Furthermore, the inactivation recovery time constant was increased after the application of propafenone, suggesting that the inhibitory action of propafenone on Kv current is partially use-dependent. Pretreatment with Kv1.5, Kv2.1 or Kv7 inhibitor did not change the inhibitory effect of propafenone on the Kv current. Together, these results suggest that propafenone inhibits the vascular Kv channels in a dose- and use-dependent manner, regardless of $Na^+$ channel inhibition.

• The Korean Journal of Pharmacology
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• v.12 no.2 s.20
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• pp.13-19
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• 1976

A fluid extract of Zizyphi Semen was employed in this experiment. The cardiac effects of Zizyphi Semen were examined on isolated rabbits atria and heart in situ of anesthetized cats and rabbits. The adrenergic blocking activity and refractory period of cardiac muscle were measured after administration of this drug. In rabbits and cats the antiarrhythmic action of Zizyphi Semen on atrial and ventricular arrhythmias produced by epinephrine or ouabain was examined. The results were following: 1. Zizyphi Semen produced a decrease in rate and contractile amplitude of the isolated rabbit atria and had a week blocking effect on epinephrine acceleration of atrial movement. 2. Zizyphi Semen effectively abolished the spontaneous arrhythmia occurring in the isolated rabbit atria ana the atrial arrhythmia induced by ouabain. 3. Zizyphi Semen produced a marked prolongation of the refractory period in isolated atrial muscle of rabbit. 4. Zizyphi Semen prevented the induction of ventricular arrhythmia arising from excessive dose of epinephrine in anesthetized rabbits and cats. 5. With regard to the ventricular arrhythmia induced by a continuous infusion of ouabain, Zizyphi Semen exerted suppressive effect and produced a marked prolongation of cardiac arrest time in anesthetized rabbits and cats. From the above results, it may be concluded that Zizyphi Semen is effective against atrial and ventricular arrhythmias. The antiarrhythmic effect of this drug may be the result of direct myocardial depressive and partially adrenergic beta receptor blocking activities including prolongation of the refractory period of cardiac muscle.

• Toxicological Research
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• v.22 no.2
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• pp.109-116
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• 2006

Safety pharmacology studies are conducted to investigated the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure in the therapeutic range and above. In the International Conference on Harmonisation (ICH), the guideline 'S7A: Safety Pharmacology Studies for Human Pharmaceuticals' has been developed and reached Step 5 of the ICH process in 2001. Now the Korea Food and Drug Administration (KFDA) are going to transfer 'The Guideline for General Pharmacology' into 'The Guideline for Safety Pharmacology'. Safety pharmacology studies should be performed in compliance with Good Laboratory Practice (GLP). Thus, the present paper reviews the Japanese GLP guidelines for pharmaceuticals to help the conduct and inspection of safety pharmacology studies in compliance with GLP. We also reviewed the ICH guidelines 'S7B revised : The Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals' and 'E14 : The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-antiarrhythmic Drugs' to apply our drug approval systems.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.112-112
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• 2003

Voltage-gated $K^{+}$ (Kv) channels represent a structurally and functionally diverse group of membrane proteins. These channels play an important role in determining the length of the cardiac action potential and are the targets for antiarrhythmic drugs. Many $K^{+}$ channel genes have been cloned from human myocardium and functionally contribute to its electrical activity. One of these channels, Kv1.5, is one of the more cardiovascular-specific $K^{+}$ channel isoforms identified to date and forms the molecular basis for an ultra-rapid delayed rectifier $K^{＋}$ current found in human atrium. Thus, the blocker of hKv1.5 is expected to be an ideal antiarrhythmic drug for atrial fibrillation. Chelidonine was isolated from Chelidonium majus L. We examined the effect of chelidonine on the hKv1.5 current expressed in Ltk-cells using whole cell mode of patch clamp techniques. Chelidonine selectively inhibited the hKv1.5 current expressed in Ltk-cells in a concentration-dependent manner, whereas did not affect the HERG current expressed in HEK-293 cells. Additionally, chelidonine reduced the tail current amplitude recorded at -50 mV after 250 ms depolarizing pulses to +60 mV, and slowed the deactivation time course resulting in a 'crossover' phenomenon when the tail currents recorded under control conditions and in the presence of chelidonine were superimposed. We found that chelidonine also inhibited the $K^{+}$ current in isolated human atrial myocytes where hKv1.5 channels were predominantly expressed. Furthermore, we examined the effects of chelidonine on the action potentials in rabbit hearts using conventional microelectrode technique. Chelidonine prolonged the action potential durations (APD) of atrial, ventricular myocytes and Purkinje fibers in a dose-dependent manner. However, the effect of chelidonine on atrial APD was frequency-dependent whereas the effect of chelidonine on the APDs of ventricular myocytes and Purkinje fibers was not frequency- dependent. Also, the selective action of chelidonine on heart was more potent than dofetilide, $K^{+}$ channel blocker.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.240.2-240.2
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• 2003

We aimed at determining bioavailability of procainarnide HCl, an antiarrhythmic drug, and developing a simple analysis in human blood using HPLC. A rapid and sensitive HPLC method was developed and validated using reverse-phase C18 column with retension time and limit of quantification of procainamide HCl being 2.58 min and 50ng/ml, respectively. Quantification was performed at 275 nm with caffeine as internal standard. The method involved a simple extraction. In order to study blood level profile in time, eight volunteers were enrolled and orally took 250 mg procainamide HCl once. (omitted)

• The Korean Journal of Medicine
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• v.99 no.1
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• pp.17-24
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• 2024

Premature atrial complex (PAC) and premature ventricular complex (PVC) are the most common arrhythmias. Most of them are benign, whereas some could be an initial sign of any underlying significant heart disease. Evaluation of daily burden and the presence of any association with underlying medical conditions are essential for proper assessment. Recently, newly developed electrocardiogram smart devices are widely available to document arrhythmias and identify correlations with symptoms. Management is required if the daily burden is high, patients are highly symptomatic, or significant structural heart disease is present. Antiarrhythmic drugs (AADs) are the first-line treatment, but if arrhythmias are drug-refractory or the patients are intolerable to AADs, catheter ablation is considered a good alternative in selected cases. In this paper, the proper diagnosis and management for PAC and PVC will be comprehensively reviewed.

• Journal of Korean Public Health Nursing
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• v.14 no.2
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• pp.431-445
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• 2000

In general the prevalence of old people is high and frequently have multiple diseases and symtoms requiring treatment. The nature of illness in the elderly has to be faced, and drugs do have an important part in the treatment of that illness. The purpose of this study were to describe health status and medication, and to provide some basic data for elderly's health education, especially for the right medication. Body mass index, self perceived health status, activities of daily living, disease and experience of past operation were surveyed to recognize the 249 elderly's actual health status. The degree of the elderly's understanding the way of medication, experience of side effects, experience of drug combination and incidence of drug adverse reaction along with drug combination were examined for medication. The aged $women(BMI; 10.7\pm13.3\%)$ overweighed the aged $men(BMI; 4.0\pm10.4\%)$. $69.0\%$ of them recognized their health good. Their activities of daily living were diminished following by the age group(p=0.0068) and relationship with self perceived health status were very significant(p=0.0005). They(192 elderly) suffered from multiple disease such as $osteoarthritis(49.5\%)$, $hypertension(32.0\%)$, gastric $disorder(16.1%)$, $diabetes(14.6\%)$, $osteomalacia(10.9\%)$, cardiovascular $disease(9.9\%)$, senile $cataract(5.7\%)$, skin $rash(5.2\%)$, liver $disease(4.2\%)$, kidney $disease(3.6\%)$, spinal cord $problem(3.6\%)$, respiratory $disease(2.1\%)$ $tuberculosis(1.0\%)\;etc(1.0\%).$ $28.3\%$ of them replied that they had an operation for appendictis senile cataract, peptic ulcer, spinal cord problem, pleurisy, hemorrhoid and the rest. Most of $them(87.4\%)$ knew the way very well how to use drugs, and $21.6\%$ of the replied 171 elderly experienced adverse drug reaction. Drug compliance rate were $high(83.6\%)$. In our study 56.9% of the 167 elderly took several medicine together. And $18.9\%$ of the 95 elderly who did drug combination had an experience of drug interaction. One person kept average 5.5 kinds of drugs at home among 243 elderly. They kept $digestives(79.4\%)$, $ointments(68.7\%)$, $vitamins(59.7\%)$, $analgesics(59.7\%)$, cold $medicines(45.3\%)$ antiarthritic $drugs(33.3\%)$, health $foods(27.7\%)$, antihypertensive $drugs(25.1\%)$, anti peptic ulcer $drugs(24.7\%)$, $laxatives(19.8\%)$, $antacids(16.5\%),\;antibiotics(l6.5\%)$, hypoglycemic $agents(10.3\%)$, cardiac $stimulants(7.0\%)$, $diuretics(4.5\%)$, antiarrhythmic $drugs(4.9\%)$, anti anginal $drugs(4.1\%)$, $hypnotics(3.3\%)$, $etc(38.3\%)$. With this result, we ascertain that polypharmacy in the elderly caused by multiple disease is common, which lead to drug interaction. So our task is to educate elderly how to use drugs in order to maximize their efficiency and to minimize their adverse effects.

• The Korean Journal of Food & Health Convergence
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• v.5 no.4
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• pp.13-17
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• 2019

Amiodarone hydrochloride is an antiarrhythmic agent which has low aqueous solubility and presents bioavailability problem. These properties are a challenge for the pharmaceutical industry. Inclusion of lipophilic compound in the hydrophobic core of micelles, i.e. self-assembled structures based on surfactants in aqueous solution, is one way of increasing the solubility. Intravenous formulation of amiodarone hydrochloride with polysorbate 80 as a detergent and benzyl alcohol as a co-solvent is used in medical practice. This paper aimed to study the effect of polysorbate 80 and benzyl alcohol on the water solubility of amiodarone hydrochloride. Formation of mixed micelles consisting of nonionic surfactant polysorbate 80 and cationic amiodarone with chloride counterion was investigated by fluorescence spectroscopy. Benzyl alcohol was found to decrease the stability of the mixed micelles and lead to crystallization of amiodarone hydrochloride. The greatest amounts of crystals formed at 4℃ for 30 days in the model drug solutions with polysorbate 80 concentrations of 100.1 mg/mL and 97.9 mg/mL. A change of the polysorbate 80 concentration and avoidance the use of benzyl alcohol are recommended to improve the stability of the parenteral dosage form. These results can open new perspectives in the optimization of amiodarone intravenous formulations.

• Archives of Pharmacal Research
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• v.28 no.3
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• pp.269-273
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• 2005

A furocoumarin derivative, psoralen (7H-furo[3,2-g][1]benzopyran-7-one), was isolated from the n-hexane fraction of Heracleum moellendorffii Hance. We examined the effects of psor-alen on a human Kv1.5 potassium channel (hKv1.5) cloned from human heart and stably expressed in Uk- cells. We found that psoralen inhibited the hKv1.5 current in a concentration-, use- and voltage-dependent manner with an IC$_{50}$ value of 180 $\pm$ 21 nM at +60 mV. Psoralen accelerated the inactivation kinetics of the hKv1.5 channel, and it slowed the deactivation kinetics of the hKv1.5 current resulting in a tail crossover phenomenon. These results indicate that psoralen acts on the hKv1.5 channel as an open channel blocker. Furthermore, psoralen prolonged the action potential duration of rat atrial muscles in a dose-dependent manner. Taken together, the present results strongly suggest that psoralen may be an ideal antiarrhythmic drug for atrial fibrillation.