Akinori Kuruma

Pharmacokinetics of landiolol hydrochloride, a new ultra‐short‐acting β‐blocker, in patients with cardiac arrhythmias

To elucidate pharmacokinetics and pharmacodynamics of landiolol hydrochloride, newer developed ultra‐short‐acting β‐blocker, in patients with various cardiac tachyarrhythmias.

Electrophysiologic and hemodynamic effects of a single oral dose of pilsicainide hydrochloride, a new class 1c antiarrhythmic agent

To establish the clinical efficacy of pilsicainide, we evaluated its electrophysiologic and hemodynamic effects after a single oral administration to 18 patients with documented supraventricular tachycardia (SVT). To determine the minimal effective blood level, changes in efficacy with time were evaluated by serial reinduction studies with venous blood sampling for measurement of the plasma pilsicainide level. Sixty minutes after administration of a single oral dose of pilsicainide, the sinoatrial conduction time, AH and HV intervals, and the effective refractory period of the right ventricle were prolonged. Ventriculoatrial conduction was blocked in 11 patients [nine of 12 via accessory pathway and two of six via the atrioventricular (AV) node], resulting in the suppression of SVT induction in nine of 13 patients. Pilsicainide increased the heart rate and mean pulmonary arterial pressure and decreased the stroke volume index at 60 min. PQ interval, QRS width, and QTc were significantly prolonged after pilsicainide, and the percentage prolongations of the PQ interval were well correlated with the plasma pilsicainide levels. The plasma level effective for suppression of SVT was considered to be >0.5 microg/ml. We concluded that a single oral administration of pilsicainide is well tolerated and effective in suppressing SVT.

Clinical and electrophysiologic effects of dofetilide in patients with supraventricular tachyarrhythmias.

The clinical and electrophysiologic effect of intravenous dofetilide was evaluated in patients with paroxysmal atrial fibrillation (AF) of recent onset (< 7 days) and paroxysmal supraventricular tachycardia (PSVT). From 2.5 to 5.0 micrograms/kg of dofetilide was administered intravenously for the termination of arrhythmias. For the electrophysiologic study (EPS), 3.0 micrograms for loading and subsequently 2 micrograms/kg was injected for 45 min as a maintenance dose. The EPSs were performed before the loading and during the maintenance dose. AF was successfully converted to sinus rhythm in seven (54%) of 13 patients. The duration of AF from its onset was significantly shorter in responders than that of nonresponders (p < 0.05). Dofetilide also terminated PSVT in four of six patients. In the EPS, dofetilide proportionately lengthened the effective refractory period of the atrium, ventricle, and the accessory pathways without slowing of the intracardiac conduction. Dofetilide completely suppressed the induction of PSVT in seven of 13 patients, restricted the induction zone in five, and inhibited perpetuation of the arrhythmia in the remaining one. The cycle length of PSVT remained unchanged after dofetilide. These results imply that the suppression of the development and maintenance of reentrant arrhythmias may result from the lengthening effect of dofetilide on the refractoriness and the consequent elimination of the excitable gap at the critical part of the reentrant loop.

Clinical effects and pharmacokinetics of a single oral dose of pirmenol hydrochloride

To establish the clinical efficacy of a single oral dose of pirmenol, we evaluated electrophysiologic and hemodynamic effects simultaneously after drug administration, performing electrophysiologic testing in 20 patients with ECG-documented paroxysmal supraventricular tachycardia (PSVT) before and after a single oral 200-mg dose of pirmenol. Hemodynamic measurements were made with a Swan-Ganz catheter in the first 10 consecutive patients. In a different series of patients, we administered a single 200-mg oral dose of pirmenol to evaluate its acute termination effect in 7 patients with PSVT and 9 with paroxysmal atrial fibrillation. Pirmenol prolonged the refractory period of the retrograde conduction system in patients with or without an accessory pathway, and supraventricular tachycardia was no longer inducible at 60 min in 11 patients [8 of 11 with atrioventricular (AV) reentrant tachycardia and 3 of 5 with AV nodal reentrant tachycardia]. Pirmenol increased the heart rate (p < 0.01) and total systemic resistance (p < 0.05), and reduced the stroke volume index (p < 0.01), all significantly. The plasma concentration of pirmenol at 1 h after administration was 0.75 +/- 0.48 microgram/ml. A single oral dose of pirmenol during tachyarrhythmia successfully restored sinus rhythm in 4 of 7 (57%) patients with PSVT and 4 of 9 (44%) patients with paroxysmal atrial fibrillation. A single oral dose of pirmenol was well tolerated as episodic treatment in patients with supraventricular tachyarrhythmias.

A Case of Cardiac Foreign Bodies Associated with Four Types of Tachycardias

A case of cardiac foreign bodies leading to development of four varieties of automatic tachycardia is reported. A 51‐year‐old male with aortic regurgitation was admitted to our hospital because of palpitations. An electrocardiogram revealed junctional tachycardia with or without left bundle branch block, and two types of fascicular tachycardias. Computed tomography showed metallic foreign bodies from a fractured guidewire in the membranous portion of the interventricular septum, which was inadvertently retained when he underwent diagnostic cardiac catheterization at the age of 27.