Biomedical subjects

Yuko Ishida

Publications and source records attributed to Yuko Ishida.

40 records · Page 3Linked to original sources

PubMed2002

Pharmacological and electrophysiological characterization of junctional rhythm during radiofrequency catheter ablation of the atrioventricular node: possible involvement of neurotransmitters from autonomic nervous system.

Catheter ablation of the atrioventricular node (AVN) with radiofrequency current is closely associated with the short-term onset of a junctional rhythm. The origin of this rhythm was analyzed in Beagle dogs which were anesthetized with pentobarbital sodium. Atrioventricular (AV) conduction block was induced first using a standard catheter ablation technique for the AVN, so that the sinus automaticity could not override the junctional ectopy during the following energy delivery. The ablation catheter was kept in the initial position and the delivery of radiofrequency energy was repeated. The pattern of ECG changes suggests that the dominant pacemaker may shift from the distal portion of the AV junctional area to the proximal portion during the energy delivery. This enhanced junctional automaticity was suppressed by the beta-blocker esmolol, but was not affected by M-antagonist atropine. Moreover, the beta-agonist isoproterenol did not induce the same type of junctional tachycardia, but the pacemaker shift was induced by the increased sympathetic tone after transient asystole by ventricular overdrive pacing or acetylcholine administration. These results suggest that proximal portion of the AV junctional area has extremely slow pacemaker activity, but responds to locally released norepinephrine with an abrupt rise and fall in rate, resulting in a typical pattern of junctional tachycardia during the ablation of the AVN.

Acetylcholine↗

PubMed2002

Comparison of the in vivo electrophysiological and proarrhythmic effects of amiodarone with those of a selective class III drug, sematilide, using a canine chronic atrioventricular block model.

Amiodarone effectively blocks both the sodium and calcium channels and beta-adrenoceptors, in addition to blocking several potassium currents including IKr, IKs, Ito, IK1, IKACh and IKNa. The incidence of clinical torsade de pointes (TdP) associated with amiodarone has been reported to be low and the present study compared the proarrhythmic potential of amiodarone with that of a selective IKr channel blocker, sematilide, using a canine chronic atrioventrucular block model. Amiodarone or sematilide (3 and 30 mg/kg; n=4 for each group) was administered orally without anesthesia under continuous ECG monitoring. Both drugs prolonged the QT interval, although the onset was faster for sematilide. The high dose of sematilide induced TdP in 3 of 4 animals, which caused their death, but neither the low dose of sematilide nor the 2 dosages of amiodarone induced lethal ventricular arrhythmias. These results suggest that IKr channel inhibition by amiodarone with its additional ion channel blocking action may contribute to the prevention of TdP.

Amiodarone↗

PubMed2002

Effects of disopyramide and mexiletine on the terminal repolarization process of the in situ heart assessed using the halothane-anesthetized in vivo canine model.

This study was designed to assess the effects of typical class I drugs on the terminal repolarization process of the in situ heart, which is a useful marker of the potential of drug-induced long QT syndrome. Disopyramide (0.3 and 3.0 mg/kg per 10 min, n = 6) or mexiletine (0.3 and 3.0 mg/kg per 30s, n = 6) was intravenously administered to halothane-anesthetized beagle dogs under the monitoring of multiple cardiovascular parameters. Antiarrhythmic concentrations were obtained with the high dose of each drug. The low dose of disopyramide or mexiletine hardly affected any of the electrophysiological parameters assessed. The high dose of disopyramide prolonged the monophasic action potential duration (MAP90) and effective refractory period (ERP) to a similar extent, thus displacing the terminal repolarization period backward, which might provide a potential proarrhythmic substrate, particularly at a slow heart rate. On the other hand, the high dose of mexiletine shortened the MAP90, but prolonged the ERP, resulting in the disappearance of the terminal repolarization period, which could prevent premature excitation with its associated conduction slowing. These electrophysiological effects of disopyramide and mexiletine on the terminal repolarization phase may at least in part explain their clinically described antiarrhythmic and proarrhythmic properties.

Action Potentials↗

PubMed2002

Electrophysiological, anatomical and histological remodeling of the heart to AV block enhances susceptibility to arrhythmogenic effects of QT-prolonging drugs.

The present study was designed to investigate what kinds of adaptation occurred in the canine chronic AV block model, which has been used to study torsade de pointes (TdP). Dogs at 7-10 days (acute phase) and 28-56 days (chronic phase) after AV block were assessed. Ventricular effective refractory period and monophasic action potential duration were prolonged in chronic animals compared with acute animals; moreover the electrically vulnerable period was prolonged in chronic animals. Non-specific IKr channel blocker cisapride (1 and 10 mg/kg, p.o.) was administered without anesthesia to estimate the feasibility of QT prolongation. In chronic animals, QT prolongation followed by TdP was induced in one dog by the low dose and in all by the high dose, which was not observed in acute animals. MR images indicated increases of diameter and wall thickness of both ventricles in chronic animals. The degree of hypertrophy was prominent in the right ventricular wall and septal wall. Heart weight of the chronic animals was 1.7 times greater than that of normal control subjects. Photo- and electron-micrograph analyses showed myocardial cell hypertrophy with parallel increases of collagen fiber and extracellular space in chronic animals. These electrophysiological, anatomical and histological adaptations may predispose the chronic AV block heart to drug-induced QT prolongation with enhanced risk of re-entry and early after depolarization, leading to the onset of TdP.

Animals↗