Enhancing effects of salicylate on quinidine-induced block of human wild type and LQT3 related mutant cardiac Na+ channels.

It is unknown whether salicylate enhances the action of antiarrhythmic agents on human Na+ channels with state dependency and tissue specificity. We therefore investigated effects of salicylate on quinidine-induced block of human cardiac and skeletal muscle Na+ channels. Human cardiac wild-type (hH1), LQT3-related mutant (ΔKPQ), and skeletal muscle (hSkM1) Na+ channel α subunits were expressed in COS7 cells. Effects of salicylate on quinidine-induced tonic and use-dependent block of Na+ channel currents were examined by the whole-cell patch-clamp technique. Salicylate enhanced the quinidine-induced tonic and use-dependent block of both hH1 and hSkM1 currents at a holding potential (HP) of -100 mV but not at -140 mV. Salicylate decreased the IC50 value for the quinidine-induced tonic block of hH1 at an HP of -100 mV, and produced a negative shift in the steady-state inactivation curve of hH1 in the presence of quinidine. According to the modulated receptor theory, it is probable that salicylate decreases the dissociation constant for quinidine binding to inactivated-state channels. Furthermore, salicylate significantly enhanced the quinidine-induced tonic and use-dependent block of the peak and steady-state ΔKPQ channel currents. The results suggest that salicylate enhances quinidine-induced block of Na+ channels via increasing the affinity of quinidine to inactivated state channels.

Exact location of the branching bundle in the living heart.

AIMS: The His bundle electrogram is believed to reflect the exact location of the His bundle. However, the distinction between distal His bundle potential and proximal right bundle branch potential is challenging. The aim of this study was to pinpoint the location of the branching point of the His bundle, and to compare that site with the site of recording of the largest His bundle electrogram (LH) during sinus rhythm. METHODS: We hypothesized that the site of earliest His activation (EH) during retrograde conduction via the left bundle branch is the branching point. We studied 15 nonconsecutive patients (mean age = 40 +/- 22 years; eight men). We performed a programmed stimulation from right ventricular apex until retrograde right bundle branch block appeared. At that point we measured (1) the distance between antegrade LH site and retrograde EH site and (2) the atrial-to-ventricular amplitude ratio (A/V ratio) at both sites. RESULTS: EH was recorded at the proximal electrode of the His bundle catheter in all patients. Mean distance between EH and LH was 9.8 +/- 2.5 mm. The mean A/V ratios at the EH site and the LH site were 1.01 +/- 0.42 and 0.08 +/- 0.06, respectively. DISCUSSION: This study showed that the EH site is located approximately 10-mm proximal to the LH site. The mean A/V ratio at the EH site during sinus rhythm is approximately 1.0. These observations suggest that the majority of His potentials reflect proximal right bundle activation. Before delivering radiofrequency energy in the para-Hisian area, attention should be paid to the presence of a His potential and to the A/V ratio, rather to the amplitude of the His electrogram.

QRS complex widening due to loss of left bundle branch capture: pitfall of para-Hisian pacing.

During para-Hisian pacing, widening of the paced QRS complex usually indicates loss of His bundle capture. We describe a patient without any accessory pathways in whom widening of the paced QRS complex occurred due to loss of left bundle branch capture during para-Hisian pacing. After initial widening of the QRS complex, further widening was observed due to loss of His bundle capture. With the initial QRS widening, the stimulus-atrial interval and retrograde atrial activation sequence were almost unchanged, so the findings mimicked retrograde conduction over an accessory pathway. This may be a pitfall of the para-Hisian pacing technique.

Left atrial branches of coronary arteries; clinical implications related to linear catheter ablation for atrial fibrillation.

BACKGROUND: Coronary artery damage has been reported during catheter ablation procedures. Recently, linear ablation of thin left atrial tissue has been performed for atrial fibrillation. OBJECTIVE AND METHODS: Because we have little information about the arteries in the left atrium, this study was performed to evaluate the anatomy of these arteries, and to compare them with previously reported ablation lines. Coronary angiography was performed in 262 patients. Atrial coronary arteries between the left atrial appendage and the left superior pulmonary vein (LAA-LSPV region), as well as between the left inferior pulmonary vein and the mitral annulus ("mitral isthmus" region) were examined. RESULTS: Atrial coronary arteries extending to the LAA-LSPV region were found in 92 subjects (35%), while arteries crossing the mitral isthmus region were found in 119 subjects (46%). Atrial coronary arteries crossed the ablation line in about 69% of subjects overall. CONCLUSION: These results might suggest a risk of acute complications due to left atrial ablation. Alternatively, recurrence of atrial fibrillation might be caused by protected myocardium around the atrial arteries. We should note that atrial coronary arteries cross the ablation line in many patients.

Long-term reliability of AAI mode pacing in patients with sinus node dysfunction and low Wenckebach block rate.

AIMS: To compare the risk of atrioventricular (AV) conduction disturbance between patients with sinus node dysfunction on AAI pacing who had a low or high Wenckebach block rate (WBR). METHODS AND RESULTS: Patients with sinus node dysfunction and normal AV conduction those underwent an electrophysiological study were studied. The patients were classified into two groups: Group L was with the patients with a WBR of 100 to 129 per minute and Group H was with the patients with a WBR > or = 130 per minute. All patients followed up every 3-6 months after an AAI pacemaker implantation. A total of 102 patients, including 35 Group L and 67 Group H, were followed for 90 +/- 44 months. Six patients died from non-cardiac cause and five patients required a new atrial lead implantation due to lead failure during follow-up. Symptomatic bradycardia requiring a new ventricular lead implantation developed in four patients (annual incidence 0.5%). In Group L, two patients developed AV block (annual incidence 0.7%). In Group H, two patients developed bradycardic atrial fibrillation (annual incidence 0.4%). Kaplan-Meier analysis revealed no significant difference between the two groups (P = 0.2983). CONCLUSION: These results suggest that a long-term risk of developing AV conduction disturbance is low even in patients with a WBR of 100 to 129 per minute.

Macroreentrant atrial tachycardia with an isolated pathway mimicking focal activation on three-dimensional electroanatomical mapping.

A 76-year-old man with two different sustained atrial arrhythmias that occurred after coronary artery bypass grafting underwent electrophysiological studies. Macroreentrant atrial tachycardias were detected with an isolated slow pathway mimicking focal activation on three-dimensional electroanatomical mapping. The slow conduction pathway in the right atrial free wall was assumed to represent tissue damaged by right atrial cannulation during previous coronary artery bypass grafting.

Atrial flutter with a large bystander segment without double potentials in the cavotricuspid isthmus.

We present two cases of common-type atrial flutter with a large bystander segment without double potentials in the cavotricuspid isthmus. In both cases, right atrial angiography demonstrated a prominent pouch at the center of the isthmus. When radiofrequency energy was applied to the tricuspid side of the isthmus, delayed potentials abruptly appeared on the local electrograms. When radiofrequency energy was applied on the inferior vena cava side of the isthmus, the tachycardia was terminated. Although ablation was not applied to the bottom of the pouch, bidirectional isthmus block was achieved. These outcomes indicate that the pouch represented a bystander segment.

Inhibition of beta-adrenergic signaling by intracellular AMP is independent of cell-surface adenosine receptors in rat cardiac cells.

We report a novel action of intracellular adenosine monophosphate (AMP) to inhibit beta-adrenergic signaling in isolated rat ventricular myocytes. Extracellular application of adenosine or AMP suppressed isoproterenol (Iso)-induced prolongation of action potential duration (APD). This effect was completely abolished by an A(1)-receptor antagonist, DPCPX. Intracellular application of AMP, but not adenosine, attenuated Iso-induced APD prolongation. Iso-induced increases in the L-type Ca(2+) current (I(Ca,L)) were also inhibited by intracellular AMP. These inhibitory effects were not affected by either DPCPX or glibenclamide. In vitro, AMP directly inhibited PKA activity via binding to its regulatory subunit. These results suggest that intracellular AMP attenuates beta-adrenergic signaling by directly inhibiting PKA activity, independently of A(1)-purinergic receptor.

Radiofrequency catheter ablation for atrial tachycardia originating from the left atrial appendage.

A 36-year-old woman presented with drug-refractory atrial tachycardia. During the tachycardia episodes, P waves were positive in leads II, III, aVF, and V1, while they were negative in leads I and aVL. It was hard to determine whether the origin was the left atrial appendage or left superior pulmonary vein on the surface electrocardiogram. Electrophysiologic evaluation revealed that the earliest endocardial activation occurred at the base of the left atrial appendage, preceding the onset of P waves by 38 ms. On initiation of the tachycardia, a warm-up phenomenon was observed. There was a fixed relation between the coupling interval of a single extrastimulus and the return cycle length during the tachycardia. These findings suggested that the mechanism of the tachycardia was automaticity. Application of radiofrequency energy at the left atrial appendage terminated the tachycardia and it was not inducible after ablation.