Kazuya Ishibashi

Kinetics of frequency-dependent conduction delay by class I antiarrhythmic drugs in human atrium.

We investigated use-dependent prolongation of interatrial conduction time (IACT) by class I antiar-rhythmic drugs in 16 patients. Changes in IACT at the initiation of atrial pacing were used to evaluate the onset kinetics. We examined recovery kinetics by giving a single extra stimulus with a varying coupling interval after discontinuing train stimulation. Time constants of the onset kinetics were 1.52 ± 0.15/n(fast) and 0.087 ± 0.031/ n(slow) for mexiletine, 0.075 ± 0.015/n for aprindine, 0.078 ± 0.019/n for disopyramide, and 0.050 ± 0.006/n for pilsicainide. The recovery time constants were 203 ± 66 ms for mexiletine, 1,021 ± 162 ms for aprindine, 993 ± 101 ms for disopyramide, and 2,930 ± 569 ms for pilsicainide. Class I antiarrhythmic drugs produced use-dependent IACT prolongation in humans, with characteristic kinetics for each agent similar to that of depression of the maximum upstroke velocity of cardiac action potential (Vmax) reported in in vitro studies.

Effects of ischemic preconditioning on the release of cardiac troponin T in isolated rat hearts.

SummaryThe aim of this study was to examine the effect of ischemic preconditioning on the releases of cardiac troponin T (TnT) during reperfusion in isolated rat hearts. Experiments were done on 22 rat hearts, which were perfused according to the method of Langendorff and were divided into the control group (n=14) and the preconditioning group (n=8). Double 5 min of ischemia each followed by 5 min reflow were applied as ischemic preconditioning. After 20 min of global ischemia, the releases of TnT, creatine kinase (CK), and lactate dehydrogenase (LD) in coronary effluent and the left ventricular developed pressure (LVP) were measured during 60 min of reperfusion. Ischemic preconditioning significantly suppressed the amounts of TnT released during reperfusion, as with those of CK and LD, and also improved contractile dysfunction (nine hearts in which ventricular fibrillation was sustained were excluded from the evaluation for hemodynamics), though the release kinetics of TnT was different from that of CK and LD. There were good inverse relationships between the LVP and the total amounts of TnT released during reperfusion period (Σ TnT) or TnT levels at 60 min of reperfusion. Cardiac TnT can be used as a useful biochemical marker for hemodynamics and myocardial damage after reperfusion.

Effects of E-4031 on atrial fibrillation threshold in guinea pig atria: comparative study with class I antiarrhythmic drugs.

The effects of E-4031, a new class III antiarrhythmic agent, on atrial fibrillation threshold (AFT), atrial effective refractory period (ERP), and interatrial conduction time (ACT) were investigated in Langendorff-perfused guinea pig hearts; the results were then compared with those of the class I agents disopyramide, procainamide, lidocaine, and flecainide. Whole guinea pig hearts were perfused with Tyrodes solution containing acetylcholine (ACh 3 x 10(-7) M). The three indexes were measured before and after administration of the test drugs, using right atrial extrastimulus and 50-Hz continuous stimulation. Disopyramide, procainamide, and flecainide (> or = 10(-6) M) significantly increased AFT. Although E-4031 (> or = 3 x 10(-6) M) also increased AFT, this effect was less potent than that observed with the other drugs. E-4031 (> or = 10(-6) M) significantly prolonged ERP, and this prolongation was less pronounced than that observed with disopyramide but similar to that observed with procainamide or flecainide. E-4031 did not affect ACT, and the greatest prolongation of ACT was observed with flecainide. Lidocaine had no effect on any of the indexes. These findings suggest that in guinea pig hearts E-4031 exerts an antifibrillatory effect by prolonging atrial ERP alone, but this effect is less pronounced than that observed with class I drugs, because AFT measured by 50-Hz continuous stimulation is influenced by both ERP and ACT.

Effects of disopyramide on the atrial fibrillation threshold in the human atrium

The effects of disopyramide on the atrial fibrillation threshold (AFT) in the human atrium were investigated. To evaluate atrial vulnerability, the following electrophysiologic parameters were measured before and after the administration of disopyramide (2 mg/kg) in 12 patients with paroxysmal atrial fibrillation: The right atrial effective refractory period (ERP) and percentage maximum atrial fragmentation (%MAF) were measured by atrial premature stimulation based on a cycle length of 500 ms. The inter-atrial conduction time (ACT) was measured by burst pacing (120/min) for 30 s. AFT was measured by applying a high-frequency (50 Hz) stimulation for 1 s given at the right atrial appendage. AFT was defined as the lowest intensity of electrical current that could induce atrial fibrillation lasting for more than 30 s. Disopyramide significantly reduced %MAF, and prolonged ERP and ACT. AFT was measured in all patients and the mean AFT was 3.1 +/- 1.7 mA. After the administration of disopyramide, AFT significantly increased to 6.1 +/- 3.6 mA. There was a positive correlation between ERP and AFT, and a negative correlation between %MAF and AFT. No correlation was detected between ACT and AFT. In conclusion, disopyramide increased AFT in the human atrium.

Myocardial stunning with partial aneurysmal formation generated during the recovering process of tachycardia-induced cardiomyopathy

We report a rare case of tachycardia-induced cardiomyopathy with apical stunning followed by partial aneurysmal formation. A 66-year-old male was admitted because of dyspnea and palpitation. Electrocardiogram showed persistent tachycardia due to atrial flutter. Echocardiography and left ventriculography showed severely diffuse hypokinesis with ejection fraction (EF) of 25%. Coronary arteries were normal. Heart failure responded well to conventional medical treatments. On day 9, persistent ST-segment elevation was disclosed before the ablation for atrial flutter. He was asymptomatic and free from the elevation of myocardial enzymes in laboratory data. (201)Tl scintigraphy showed slight hypoperfusion at a narrow site of the apex, whereas (123)I-betamethyl-iodophenyl-pentadecanoic acid scintigraphy revealed complete defect in the apical area. Left ventriculography showed akinesis at the localized site in the apex and mild hypokinesis in the basal area, with EF of 43%. However, no abnormalities were detected in coronary arteries during the ST-segment elevation. After 3 months, left ventriculography revealed the aneurysmal formation at a part of the apex, with EF of 50%, although the apical movement was improved. Moreover, coronary spasm was not induced by the intracoronary injection of ergonovine. In this case, a mechanism similar to Tako-Tsubo cardiomyopathy was speculated for the apical stunning.

Electrophysiological effects of flecainide acetate on stretched guinea pig left atrial muscle fibers

SummaryThe electrophysiological effects of flecainide acetate (3×10−6 M) on stretched atrial tissue were investigated using guinea-pig left atrial muscle fibers. Before stretching, the resting membrane potential was not affected by flecainide at 1 Hz, although the overshoot potential (Eov) and the action potential duration at 50% repolarization (APD50) were slightly but significantly decreased by 2±1 mV and 2±1 msec, respectively. The effective refractory period (ERP) was increased by 3±1 msec. The reduction of

Brugada syndrome associated with J waves in multiple leads and ''pseudo-epsilon'' wiggle waves in lateral leads: Possible conduction delay in J-wave syndrome

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Idiopathic Long QT Syndrome With Early Afterdepolarization Induced by Epinephrine

max was 20.6±1.2%. The half-maximum potential (Vh) of the relationship between