발작성 상심실성 빈맥 환자에 대한 항부정맥 약물작용 기전과 약물반응 예측에 관한 연구

김병옥(Byung Ok Kim),김성순(Sung Soo Kim),황성오(Sung Oh Whang),장양수(Yang Soo Jang),심원흠(Won Heum Shim),조승연(Seung Yun Cho),김현승(Hyun Seung Kim),박승정(Seung Jung Park) 대한내과학회 1990 대한내과학회지 Vol.39 No.6

N/A In this study, the effects of antiarrhythmic drugs on the reentrant pathway in paroxysmal supraventricular tachycardia (PSVT) were evaluated by observing the changes of conduction block cycle length. And this study was aimed to determine whether the drug responses could be predicted by characterizing the reentry path- way. Seventy-three patients with clinically documented PSVT without preexcitation were carried on electro-physiologic studies between November, 1986 and April 1990 in Severance Hospital, Yonsei University were reviewed. The study group included 35 males and 38 females with ages ranging from 16 to 67 years (mean±SD:40±15). The mean duration of symptom was 10.9±9.5 years. They had experienced paroxysmal tachycardia once per week to once in 6 months (mean frequency: 5 per year). All patients had structurally normal heart except the 2 Ebstein`s anomaly. The induction of tachycardia and the determination of mechanism of PSVT were performed by baseline electrophysiologic study in drug free status, The effects of drugs were assessed by the intravenous administration of procainamide 20 mg/kg, flecainide 2 mg/kg, verapamil 0.15 mg/kg, digoxin 0.75 mg, and digoxin 0,75 mg plus propranolol 0.15 mg/kg. The response to drug was defined as the not-induced SVT or the induction of nonsustained SVT after drug administration. 1) Fourty-nine patients had atrioventricular (AV) reentrant tachycardia using concealed bypass tract(CBT) and twenty-four patients had atrioventricular nodal reentrant tachycardia. In AV reetry using CBT, procainamide prevented induction of sustained tachycardia in 38 of 45 patients (84%), flecainide in 23 of 30 patients(77%), verapamil in 34 of 39 patients(87%), digoxin in 4 of 17 patients (23%), and digoxin plus propranolol in 7 of 14 patients(50%), In AV nodal reentry, procainamide prevented induction of sustained tachycardia in 19 of 22 patients (86%), flecainide in 9 of 10(90%), verapamil in 20 of 22 patients(91%), digoxin in 10 of 17 patients(59%), and digoxin plus propranolol in 9 of 13 patients(69%). 2) In AV reentry using CBT, procainamide and flecainide induced significant prolongation of the ventriculoatrial block cycle length (VABCL) in responder group. Also the atriventricular block cycle length (AVBCL) was prolonged significantly, but not increased above the tachycardia cycle length. Verapamil, digoxin and digoxin plus propranolol showed significant prolongation of AVBCL, but not of VABCL. 3) In AV nodal reentry, procainamide and flecainide induced significant prolongation of VABCL in responder group, and AVBCL was also prolonged but not increased above the tachycardia cycle length. Verapamil, digoxin and digoxin plus propranolol induced significant prolongation of both AVBCL and VABCL in responder group. 4) In patients with AV reentry, there was no significant difference of baseline VA block cycle length between responders and non-responders for procainamide and flecainide. But the patients having the 260 millisecond or more of block cycle length were all responded to procainamide except 1 case and all to flecainide. 5) The procainamide and flecainide had a strong concordant relationship in drug response for AV reentry(p<0. 001). With the avove results, it is noted that the procainamide and flecainide prevent induction of reentrant supraventricular tachycardia by selectively depressing the conduction over retrograde pathway of reentry circuits in responders with AV reentry using CBT and AV nodal reentry. Also it is noted that the verapamil, digoxin and digoxin plus propranolol prevented induction of SVT by depressing the conduction over antegrade pathway in responders with AV reentry using CBT, and over antegrade (AV nodal slow) and retrograde (AV nodal fast) pathways in responders with A V nodal reentry. And it can be suggested that the baseline block cycle length of accessory pathway has a limited value in predicting the drug responses in AV reentry using CBT. Also it is noted that in AV r

Synthesis of Psoralen Derivatives and Their Blocking Effect of hKv1.5 Channel

Eun, Jae-Soon,Kim, Kwang-Sik,Kim, Han-Na,Park, Seon-Ah,Ma, Tian-Ze,Lee, Kyung-A,Kim, Dae-Keun,Kim, Hyung-Kyo,Kim, In-Su,Jung, Young-Hoon,Zee, Ok-Pyo,Yoo, Dong-Jin,Kwak, Yong-Geun 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.2

Previously, we found that a furocoumarin derivative, psoralen (7H-furo[3,2-g][1 ]benzopyran-7-one), blocked a human Kv1.5 potassium channel (hKv1.5) and has a potential antiarrhythmic effect. In the present study, to develop more potent hKv1.5 blockers or antiarrhythmic drugs, we synthesized ten psoralen derivatives and examined their blocking effects or hKv1.5 stably expressed in Ltk cells. Among the newly synthesized psoralen derivatives, three derivatives (Compounds 5,9 and 10) showed the open channel-blocking effect. Compound 9 among them was the most potent In blocking hKv1.5. We found that compound 9, one of the psoralen derivatives, inhibited the hKv1.5 current in a concentration-, use- and voltage-dependent manner with an IC$_{50}$ value of 27.4 ${\pm}$ 5.1 nM at +60 mV. Compound 9 accelerated the inactivation kinetics of the hKv1.5 channel, slowed the deactivation kinetics of hKv1.5 current resulting in a tail crossover phenomenon. Compound 9 inhibited hKv1.5 current in a use-dependent manner. These results indicate that compound 9, one of psoralen derivatives, acts on hKv1.5 channel as an open charnel blocker and is much more potent than psoralen in blocking hKv1.5 channel. If further studios were done, compound 9 might be an ideal antiarrhythmic drug for atrial fibrillation.

Synthesis of Psoralen Derivatives and Their Blocking Effect of hKv1.5 Channel

은재순,김광식,김한나,박선아,Tian-Ze Ma,이경아,김대근,김형교,김인수,정영훈,지옥표,유동진,곽용근 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.2

Previously, we found that a furocoumarin derivative, psoralen (7H-furo[3,2-g][1]benzopyran-7- one), blocked a human Kv1.5 potassium channel (hKv1.5) and has a potential antiarrhythmic effect. In the present study, to develop more potent hKv1.5 blockers or antiarrhythmic drugs, we synthesized ten psoralen derivatives and examined their blocking effects on hKv1.5 stably expressed in Ltk- cells. Among the newly synthesized psoralen derivatives, three derivatives (Compounds 5, 9 and 10) showed the open channel-blocking effect. Compound 9 among them was the most potent in blocking hKv1.5. We found that compound 9, one of the psoralen derivatives, inhibited the hKv1.5 current in a concentration-, use- and voltage-dependent manner with an IC50 value of 27.4 ± 5.1 nM at +60 mV. Compound 9 accelerated the inactivation kinetics of the hKv1.5 channel, slowed the deactivation kinetics of hKv1.5 current resulting in a tail crossover phenomenon. Compound 9 inhibited hKv1.5 current in a use-dependent manner. These results indicate that compound 9, one of psoralen derivatives, acts on hKv1.5 channel as an open channel blocker and is much more potent than psoralen in blocking hKv1.5 channel. If further studies were done, compound 9 might be an ideal antiarrhythmic drug for atrial fibrillation.

Effects of Psoralen Derivatives on hKv1.5 Current

Jae Soon Eun,Dae Keun Kim,Jae Yoon Leem,Kyung A Lee,Hoon Park,Jin Kwon,Young Hoon Jung,Yong Geun Kwak 한국응용약물학회 2006 Biomolecules & Therapeutics(구 응용약물학회지) Vol.14 No.2

Effects of Oxypeucedanin on hKv1.5 and Action Potential Duration

Eun, Jae Soon,Park, Jung Ah,Choi, Bok Hee,Cho, Sun Kyung,Kim, Dae Keun,Kwak, Yong Geun Pharmaceutical Society of Japan 2005 BIOLOGICAL & PHARMACEUTICAL BULLETIN Vol.28 No.4

<P>A furocoumarin derivative, oxypeucedanin, was purified from <I>Angelica dahurica</I>, and its effects on the human Kv1.5 (hKv1.5) channel and on the cardiac action potential duration (APD), were examined using the patch-clamp technique and the conventional microelectrode technique. Oxypeucedanin inhibited the hKv1.5 current in a concentration-dependent manner, with an IC<SUB>50</SUB> value of 76 n<SMALL>M</SMALL>, while it had no effect on human eag-related gene (HERG) current. Oxypeucedanin induced an initial fast decline of hKv1.5 current during depolarizations. The inhibition of hKv1.5 channel by oxypeucedanin was voltage-dependent, especially at depolarizing pulses between −40 and 0 mV which corresponds to the voltage range of the channel's opening. Oxypeucedanin also slowed the deactivation time course, resulting in a tail crossover phenomenon. Additionally, oxypeucedanin prolonged the APD of rat atrial and ventricular muscles in a dose-dependent manner. These results suggest that oxypeucedanin is a kind of open-channel blocker of the hKv1.5 channel and it prolongs the APD; therefore, it is an excellent candidate as an antiarrhythmic drug for atrial fibrillation.</P>

The Effects of a Bidirectional Cavo-Tricuspid Isthmus Block in Persistent Atrial Fibrillation

김진배,이문형,최성훈,정보영,김성순 연세대학교의과대학 2012 Yonsei medical journal Vol.53 No.1

Purpose: Hybrid therapy with catheter ablation of the cavo-tricuspid isthmus (CTI) and continuation of anti-arrhythmic drugs (AAD), or electrical cardioversion with AADs might be alternative treatments for patients with persistent atrial fibrillation (AF). The goal of study was to assess the long term success rate of hybrid therapy for persistent AF compared to antiarrhythmic medication therapy after electrical cardioversion and identify the independent risk factors associated with recurrence after hybrid therapy. Materials and Methods: A total of 32 patients with persistent AF who developed atrial flutter after the administration of a class Ic or III anti-arrhythmic drug were enrolled. This group was compared with a group (33 patients) who underwent cardioversion and received direct current cardioversion with AADs. Baseline data were collected, and electrocardiogram and symptom driven Holter monitoring were performed every 2-4 months. Results: There was no significant difference in the baseline characteristics between the groups. The 12 month atrial arrhythmia free survival was better in the hybrid group, 49.0% vs. 33.1%, p=0.048. However, during a mean 55.7+/- 43.0 months of follow up, the improved survival rate regressed (p=0.25). A larger left atrium size was an independent risk factor for the recurrence of AF after adjusting for confounding factors. Conclusion: Despite favorable outcome during 12 month, the CTI block with AADs showed outcomes similar to AAD therapy after electrical cardioversion over a 12 month follow up period. Minimal substrate modification with AADs might be an alternative treatment for persistent AF with minimal atrial remodeling.