Yuji Kasaoka

Short-term effects of rapid pacing on mRNA level of voltage-dependent K(+) channels in rat atrium: electrical remodeling in paroxysmal atrial tachycardia.

BACKGROUND Atrial fibrillation causes electrophysiological changes of the atrium, thereby facilitating its maintenance. Although the expression of ion channels is modulated in chronic atrial fibrillation, it is yet unknown whether paroxysmal atrial fibrillation can also lead to electrical remodeling by affecting gene expression. METHODS AND RESULTS To examine the short-term effects of rapid pacing on the mRNA level of voltage-dependent K(+) channels, high-rate atrial pacing was performed in Sprague-Dawley rat hearts. Total RNA was prepared from the atrial appendages from 0 to 8 hours after the onset of pacing, and mRNA levels of Kv1.2, Kv1. 4, Kv1.5, Kv2.1, Kv4.2, Kv4.3, erg, KvLQT1, and minK were determined by RNase protection assay. Among these 9 genes, the mRNA level of the Kv1.5 channel immediately and transiently increased, with bimodal peaks at 0.5 and 2 hours after the onset of pacing. Conversely, the pacing gradually and progressively decreased the mRNA levels of the Kv4.2 and Kv4.3 channels. The increase of Kv1.5 and the decrease of Kv4.2 and Kv4.3 mRNA levels were both rate dependent. In correspondence with the changes in the mRNA level, Kv1. 5 channel protein transiently increased in the membrane fraction of the atrium during a 2- to 8-hour pacing period. Electrophysiological findings that the shortening of the action potential produced by 4-hour pacing was almost abolished by a low concentration of 4-aminopyridine implied that the increased Kv1.5 protein was functioning. CONCLUSIONS Even short-term high-rate atrial excitation could differentially alter the mRNA levels of Kv1.5, Kv4.2, and Kv4.3 in a rate-dependent manner. In particular, increased Kv1.5 gene expression, having a transient nature, implied the possible biochemical electrical remodeling unique to paroxysmal tachycardia.

His‐Bundle Parasystole Masquerading as Exercise‐Induced 2:1 Atrioventricular Block

His‐Bundle Parasystole. We describe a case of symptomatic pseudo‐AV block due to His‐bundle parasystole masquerading as exercise‐induced 2:1 AV block. Electrophysiologic study revealed the presence of His‐bundle parasystole, and the fluctuation of parasystolic cycle length could be explained by the concept of modulated parasystole. Modulated parasystole is a possible explanation for maintenance of stable 2:1 AV conduction at an atrial rate of specific range during exercise.

Site of the Arrhythmogenic Focus and Cardiac Vulnerability to Ventricular Fibrillation

MURAKAWA, Y., et al.: Site of the Arrhythmogenic Focus and Cardiac Vulnerability to Ventricular Fib‐rillation. The aim of this study was to test the hypothesis that a subendocardial arrhythmogenic focus makes the heart more susceptible to VF due to electrical interaction with the Purkinje network. Monofocal ventricular tachycardia (mVT) was created by injecting 5‐μg aconitine into the left ventricular subepicardium (EPI‐mVT, n = 8) or subendocardium (ENDO‐mVT, n = 13) in anesthetized dogs. Despite the similar cycle length of mVT, the incidence of VF was significantly different between EPI‐mVT and ENDO‐mVT (100 [8/8] vs 46% [6/13], P < 0.05). VF was invariably preceded by hemodynamic deterioration. Three‐dimensional cardiac mapping (n = 10, 221 ± 11 recording sites) revealed that VF was triggered solely by focal firing unrelated to the primary arrhythmogenic focus in both mVT models. No interaction between the primary focus and adjacent endocardial tissue was indicated. These results suggest that the proximity of the arrhythmogenic focus to the Purkinje network has little role in cardiac vulnerability to VF, and that progression of mVT to VF is largely caused by sporadic focal firing regardless of the site of the arrhythmogenic focus in the present animal model.