The Myocardial Lesions Produced by the Potassium Channel Opener Aprikalim in Monkeys and Rats Are Prevented by Blockade of Cardiac {beta}-Adrenoceptors

Aprikalim is a potent, specific, and selective opener of ATP-sensitiveK⁺ (K_ATP) channels. By virtue of this pharmacological property,aprikalim affords cardioprotection in experimental models ofischemia/reperfusion injury, and, at higher doses, also causesperipheral or coronary vasodilatation. Direct-acting peripheralvasodilators can cause myocardial lesions, particularly in ratsand dogs. However, unexpectedly, aprikalim produced this effectalso in monkeys. Thus, the primary aim of this investigationwas to assess whether in monkeys these myocardial lesions werethe direct or indirect consequence of the vascular effects ofaprikalim. Cyno-mologus monkeys were given the ß-adrenoceptorantagonist nado-lol (2 mg/kg po, twice daily) for 4 consecutivedays. On the third and fourth day of the experiment, they receivedaprikalim (1 mg/kg po). In another series, two monkeys carryingtelemetry transmitters for blood pressure and heart rate measurementswere also given aprikalim or its vehicle. Finally, aprikalim(1 mg/kg po for 2 days) or its vehicle was administered to ratswhich were concurrently treated with the ß-adrenoceptorantagonist atenolol (5 mg/ kg sc) or its vehicle. In cynomologusmonkeys, aprikalim produced focal and multifocal myocardialnecrosis of minimal to moderate intensity in or near the papillarymuscles of the left ventricle. These effects were abrogatedby nadolol. Similarly, necrotic lesions were caused by aprikalimonly in those rats which had not been pretreated with atenolol.In monkeys, aprikalim produced a marked and long-lasting decreasein aortic blood pressure, accompanied by an even more prolongedtachycardia. These results demonstrate that aprikalim can producemyocardial necrosis not only in rats but also in monkeys. Toour knowledge, this is the first time that such adverse effectsare reported for a vasodilator in monkeys. More importantly,these effects were prevented by blocking cardiac ß-adrenoceptors.Thus, the myocardial lesions produced by aprikalim may be attributedto its profound and prolonged hemodynamic effects.     

Left Ventricular Diastolic Dysfunction in Atrial Fibrillation: Predictors and Relation with Symptom Severity

Left Ventricular Diastolic Dysfunction in Atrial Fibrillation Background: Left ventricular diastolic dysfunction (LVDD) is common in the general population, but its prevalence in atrial fibrillation (AF), predictors for LVDD in AF and the association between LVDD and AF‐related symptom severity has not been well studied. Methods: In 124 consecutive patients (mean age 61 ± 11years, 60% male) with paroxysmal (n = 70) or persistent AF (n = 54) referred for AF catheter ablation, LVDD was evaluated according to current guidelines using transthoracic echocardiography. AF‐related symptom severity was quantified using the European Heart Rhythm Association score. Results: LVDD was present in 46 patients (37%). In uni‐ and multivariable regression analysis, age (OR 1.068 per year, 95% CI 1.023–1.115, P = 0.003) and persistent AF (OR 2.427 vs. paroxysmal AF, 95% CI 1.112–5.3, P = 0.026) were associated with LVDD. LVDD was found in 11% with mild AF symptoms (n = 27) as opposed to 44% in patients with moderate–severe AF symptoms (n = 97, P = 0.002). Thus, the OR for moderate–severe AF symptoms was 6.368 (1.797–22.568, P = 0.004) in the presence of LVDD. Conclusions: LVDD (1) occurs frequently in AF, (2) is associated with advancing age and AF progression and (3) is correlated with symptom severity in AF. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1073‐1077, October 2012)     

Relation Between Left Atrial Size and Secondary Atrial Arrhythmias After Successful Catheter Ablation of Common Atrial Flutter

Catheter ablation ptovides an effective cure for patients with typical atrial flutter. However, these patients may have the potential to develop atrial tachyarrhythmias other than common atrial flutter. This study examines clinical and echocardiographic predictors for the occurrence of uncommon atrial flutter or atrial fibrillation after abolition of common atrial flutter. The study population comprised 17 patients (12 men, 5 women, age 32–74 years) who underwent successful radiofrequency catheter ablation of common atrial flutter. Common atrial flutter did not recur in any patient during a median follow-up time of 8 (range 1–25) months. Within a median of 7 (range 1–223) days, however, symptomatic atrial tachyarrhythmias occurred in 8 of 17 patients (47%): uncommon atrial flutter (n = 4); atrial fibrillation (n = 3); and both uncommon atrial flutter and atrial fibrillation in one patient. Preablation left atrial volume was significantly larger in patients who developed secondary arrhythmias compared with patients who remained in sinus rhythm (57.9 ± 15.6 vs 43.7 ± 16.4 cm³, P < 0.05). Enlarged left atrial volume dichotomized at 51 cm³ independently predicted postablation atrial arrhythmias (x²=5.11, rel. risk = 5.3, P < 0.05). On Kaplan-Meier analysis, time to occurrence of postablation atrial arrhythmias was significantly shorter in patietits with enlarged left atrium (P < 0.02). In conclusion, symptomatic uncommon atrial flutter and atrial fibrillation develops in a substantial proportion of patients after successful ablation of common atrial flutter. Out of a series of clinical and echocardiographic parameters, preablation left atrial size is the best predictor for the occurrence of these postablation atrial arrhythmias.     

Radiofrequency Catheter Ablation of Idiopathic Left Ventricular Tachycardia:

Idiopathic Left Ventricular Tachycardia. Introduction: Idiopathic left ventricular tachycardia with a QRS pattern of right bundle branch block and left-axis deviation constitutes a rare but electrophysiologically distinct arrhythmia entity. The underlying mechanism of this tachycardia, however, is still a matter of controversy. This report describes findings in a 42-year-old man who underwent successful radiofrequency catheter ablation of idiopathic left ventricular tachycardia.
Methods and Results: On electrophysiologic study, the tachycardia was reproducibly induced and terminated with double ventricular extrastimuli. Intravenous verapamil terminated the tachycardia whereas adenosine did not. Detailed left ventricular catheter mapping during sinus rhythm revealed a fragmented delayed potential at the mid-apical region of the inferior site near the posterior fascicle of the left bundle branch. At the same site, continuous electrical activity throughout the entire cardiac cycle was recorded during ventricular tachycardia. Repeated spontaneous termination of this continuous electrical activity in late diastole was followed immediately by termination of the tachycardia. Single application of radiofrequency current for 20 seconds at this site completely abolished inducibility of the tachycardia. After catheter ablation, at the identical site of preablation recording of the fractionated potential during sinus rhythm, no fragmented delayed activity could be recorded. There was no complication from the ablation procedure.
Conclusion: The preablation recordings of fragmented delayed potentials during sinus rhythm and continuous diastolic electrical activity during tachycardia, together with ablation characteristics and previously reported electrophysiologic properties of this arrhythmia, may further support microreentry as the underlying mechanism in idiopathic left ventricular tachycardia.     

Phrenic Nerve Stimulation for Central Ventilatory Failure with Bipolar and Four-Pole Electrode Systems

A multi-channel phrenic nerve stimulator developed in Tampere has been implanted into seven patients with C2-tetraplegia and into three patients with central sleep apneas. Six bipolar cuff electrodes were implanted bilaterally into the neck. Two four-pole cuff and 14 four-pole noncuff electrodes were used in seven patients and to replace one bipolar electrode. Four-pole electrodes were implanted within the thorax. Seven patients achieved total independence from conventional ventilators within 4 months of implantation, and one for 18 hours each day. Two patients died 12 days and 3 months after implantation and two patients after having achieved independence from mechanical ventilators from causes unrelated to the stimulators. Reoperations were necessary because of dislocation of receivers, electrodes, electrode lesions, nerve injuries, and technical failures in seven patients. Most of the problems appeared in two patients with obesity and in three patients with very thin phrenic nerves. Single unit prototypes failed technically more frequently than units of prototype serial fabrication. New electrode design, progress in the manufacture of receivers, and improved implantation technique should help to diminish failures in future.     

Atrial Arrhythmias in Long-QT Syndrome under Daily Life Conditions: A Nested Case Control Study

Background: The long-QT syndromes (LQTS) are inherited electrical cardiomyopathies characterized by prolonged ventricular repolarization and ventricular arrhythmias. Several genetic reports have associated defects in LQTS-causing genes with atrial fibrillation (AF). We therefore studied whether atrial arrhythmias occur in patients with LQTS under daily-life conditions.
Methods: We systematically assessed atrial arrhythmias in LQTS patients and matched controls using implanted defibrillators or pacemakers as monitors of atrial rhythm in a nested case-control study. Twenty-one LQTS patients (3 male; 39 ± 18 years old; 18 on β blocker, ICD therapy duration 6.3 ± 2.7 years; 4 LQT1, 6 LQT2, 2 LQT3) were matched to 21 control subjects (13 male; 50 ± 19 years old; 3 on β blocker; pacemaker therapy duration 8.5 ± 5.5 years; 19 higher-degree AV block, 2 others). LQTS patients were identified by a systematic search of the LQTS patient databases in Münster and Munich.
Results: One-third (7 of 21) of the LQTS patients developed self-terminating atrial arrhythmias (atrial cycle lengths <250 ms). Only one control patient developed a single episode of postoperative AF (P < 0.05 vs LQTS).
Conclusions: LQTS patients at high risk for ventricular arrhythmias may develop short-lasting atrial arrhythmias under daily-life conditions, suggesting that prolonged atrial repolarization may contribute to the initiation of AF.     

Initial Clinical Experience with the New Irrigated Tip Magnetic Catheter for Ablation of Scar-Related Sustained Ventricular Tachycardia: A Small Case Series

Background: A remote magnetic navigation system (MNS) has been used with a nonirrigated magnetic catheter for ablation of some supraventricular and ventricular arrhythmias. However, the irrigated tip catheter has not been evaluated.
Objective: To evaluate the feasibility and efficiency of the newly available irrigated tip magnetic catheter for radiofrequency ablation (RF) of electrical storm due to scar-related ventricular tachycardia (VT) in patients with ischemic heart disease.
Methods: Between January and March 2008, a total of 4 consecutive patients (4 men, mean age 67.7 years) with electrical storm who had an implantable cardioverter defibrillator underwent radiofrequency ablation using a remote MNS and the new magnetic irrigated catheter.
Results: Five ablation procedures were performed in study patients. Acute success, defined as noninducibility of any monomorphic VT, was obtained in 3 patients. In 1 patient, a nonclinical VT remained inducible. A monomorphic VT corresponding to clinical VT with the median (range) cycle length of 485 (440–580) ms was induced in all patients. The duration of ablation was 2,273 (985–3087) seconds, with median total procedure and fluoroscopy times of 135 (100–150) minutes and 6.5 (5–9) minutes, respectively. One recurrence occurred 1 week after ablation, which was ablated successfully in the second session. No complication was observed after ablation. During mean follow-up of 4.2 months, all patients were in sinus rhythm, they received no ICD therapy, and no mortality occurred.
Conclusions: Irrigated ablation of scar-related ventricular tachycardia guided by remote MNS is a feasible and effective modality for management of the electrical storm in patients with ischemic cardiomyopathy with minimal radiation exposure.     

Unexpected Emergence of Manifest Preexcitation Following Transcatheter Ablation of Concealed Accessory Pathways

Preexcitation After Catheter Ablation. Introduction: The basis for anterograde or retrograde unidirectional block of accessory pathways still remains a controversial issue.
Methods and Results: Four of 19 consecutive patients (1 mule, 3 Female; ages 27 to 34 years) who underwent transcatheter ablation of concealed accessory pathways developed manifest preexcitation after the ablation. The location of the concealed accessory pathways in these four patients were right lateral, left posteroseptal, left posterolateral, and left lateral. Radiofrequency current was used in three of the four patients and high energy direct current in one patient. After ablation, manifest preexcitation was observed in these four patients for the first time. Manifest preexcitation developed immediately after ablation in two of the four patients and after 4 and 14 days in the other two. Detailed endocardial mapping revealed that the manifest preexcitation originated from the same location as the concealed pathways. Subsequently, catheter ablation was successfully performed in three of the four patients using radiofrequency current. One patient underwent successful surgical ablation. No recurrence of preexcitation was observed during a follow-up period of 9 to 38 months. All patients remained free of arrhythmias.
Conclusion: The basis for this unexpected emergence of preexcitation in these patients with only retrograde conducting accessory pathways deserves further investigation. Although not compared in the present study, this phenomenon has not been reported in patients who underwent surgical interruption of accessory pathways. We postulate that a lesion at the site of insertion of the accessory pathway had modified the anterograde conduction capacity.     

Characterization of putrescine transport across the intestinal epithelium: study using isolated brush border and basolateral membrane vesicles of the enterocyte

Abstract. Putrescine transport was investigated in isolated brush border and basolateral membrane vesicles prepared from the rabbit enterocyte. Brush border vesicles were oriented right-side-out and basolateral vesicles inside-out, forming a model representing uptake and extrusion across the intestinal epithelium. Putrescine transport across both membranes was initially rapid, and 66% of the equilibrium uptake was achieved within the first minute. According to osmo-plots and measurements at 4C, 20% of total incorporation presented binding to the membrane. In order to estimate actual uptake into the vesicles, K_m was calculated from the differences in putrescine incorporation at 37C and 4C, and was 12.7 μmol L^-1 for brush border uptake and 38.2 μmol L^-1 for basolateral extrusion. Putrescine uptake into brush border and basolateral membrane vesicles was not enhanced in the presence of an Na⁺ gradient. When Na⁺ was substituted with an uncharged solute, mannitol, putrescine incorporation was increased, indicating that putrescine uptake is not Na⁺-dependent and that cations might interfere with the carrier. Paraquat and methylglyoxal-bis(guanylhydrazone), known to share the polyamine transport system, inhibited putrescine incorporation in both membrane vesicle preparations. Basolateral carrier showed significantly higher sensitivity to cations. We conclude that putrescine uptake across the apical membrane and extrusion across the basolateral membrane of the enterocyte are mediated by two different and independent carriers which differ in their electrical properties.     

Three-Dimensional Electromagnetic Catheter Technology:

Electroanatomical Mapping. Introduction : The difficult catheter orientation and navigation associated with conventional technology and mono-/multiplane fluoroscopy may complicate ablation procedures of atrial tachycardias. A new three-dimensional catheter technology for electroanatomical mapping of the right atrium and ablation of ectopic atrial tachycardia is described.
Methods and Results : A novel electromagnetic catheter-based mapping system was investigated for electroanatomical mapping of the entire right atrium in 12 patients. The system reconstructed three-dimensional maps from the multitude of endocardial sites that were sequentially mapped and color coded the individual activation times. The electrophysiologic information was superimposed on the geometry of the mapped area. The anatomical landmarks of the right atrium, i.e., the tricuspid annulus. mouth of the coronary sinus, ostia of the superior and inferior venae cavae, and right atrial appendage, could he depicted in all cases. The sinus node area and the preferential conduction along the crista terminalis could be delineated. In four patients with ectopic atrial tachycardia, the earliest endocardial activation could be identified with high spatial resolution as a "hot spot." After completion of the mapping procedure, the ablation catheter could be reliably renavigated to the site of origin, and ablation was successful with one or two impulses. In one patient with previous atrial septal repair, the activation map allowed the reconstruction of a long line of conduction block induced by the atriotoniy.
Conclusion : Three-dimensional electroanatomical mapping of the right atrium allowed detailed reconstruction of the chamber geometry and activation sequence. The sites of origin of ectopic atrial tachycardias could be identified precisely. The system allowed accurate renavigation to the site of earliest activation, thereby guiding successful ablation of the foci.