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Notes: We have described the value of the diastolic slope of the MAP recording at the end of a pacing train as a qualifying marker for the induction of delayed afterdepolarization (DAD) dependent arrhythmias. In the present study (1) the behavior of the slope at different time points during a pacing train was quantified and related to the arrhythmogenic outcome (group A) and (2) termination of DAD dependent VT was related to changes in the slope steepness (group B). In dogs with chronic complete AV block, a MAP was recorded during (1) ventricular pacing, before and after ouabain administration (group A) and (2) 6 spontaneous and 6 lidocaine induced VT terminations (group B). During control (group A), the slope at the end of pacing train was 5 ± 3 mV/s (mean ± SD), independent of the pacing duration. During ouabain, this increased to 20 ± 15 mV/s (P 〈 0.05), varying with the duration of pacing. The slope was steeper after pacing for 4 seconds, compared to 20 seconds (26 ± 12 mV/s vs 16 ± 13 mV/s, P 〈 0.05) which corresponded with more frequent VT induction. In spontaneously terminating VTs (group B), CL increased from 353 ± 54 ms at the start to 434 ± 78 ms (P 〈 0.05) before VT termination. This corresponded with a decreasing steepness of the slope from 19 ± 10 mV/s to 6 ± 5 mV/s (P 〈 0.05). In lidocaine induced VT termination, the CL and the steepness of the slope showed an identical behavior. There is a dynamic variation in the steepness of the diastolic slope during pacing, which depends on the duration of pacing and predicts arrhythmogenic outcome. Furthermore, a decrease in steepness of the slope during DAD dependent VT can be used to predict VT termination.

Notes: Mechanism-Specific Action of Levcromakalim. Introduction: The hypothesis that levcromakalim. a potassium channel (IK-ATP.) activator with antihypertensive properties, has a mechanism-specific antiarrhythmic action against repolarization-dependent ventricular tachycardias (VTs) was tested in dogs. Methods and Results: A low dose of leveromakalim (0.01 mg/kg) was selected, which decreased blood pressure by 25% but had almost no electrophysiologic effect on AV nodal or ventricular conduction or effective refractory period. In dogs with chronic AV block, the antiarrhythmic action of this dose of levcromakalim was evaluated in three models of abnormal impulse formation: (I) dsotalol (2 mg/kg) induced torsades de pointes VT, initiated by early afterdepolarizations (EADs). (2) sustained ouabain-induced VTs, which are dependent on delayed after depolarizations (DADs), and (3) VT occurring 24 hours after left anterior descending coronary artery occlusion, which are likely based on abnormal automaticity. Levcromakalim abolished d-sotalol induced U waves, ventricular ectopic beats, and self-terminating bouts of torsades de pointes. Induction of torsades de pointes by pacing was also completely prevented. The cycle length of the idioventricular rhythm, which was lengthened after d-sotalol from 1490 ± 515 to 1700 ± 610 msec (P 〈 0.05), remained similar after levcromakalim (1655 ± 580 msec). The QT(U) duration, which was increased after d-sotalol from 410 ± 55 to 550 ± 40 msec (P 〈 0.05), normalized to 405 ± 70 msec (P 〈 0.05). Lcvcromakulim did not suppress but rather enhanced ouabain-induced VT by decreasing the cycle length slightly from 315 ± 35 to 290 ± 35 msec (P 〈 0.05). Pretreatment with a beta Mocker prevented this acceleration in rate. Finally, levcromakalim had no effect on VT 24 hours after infarction. Conclusion: A low dose of levcromakalim has specific antiarrhythmic properties against repolarization-dependent arrhythmias, but it does not affect VTs based on other mechanisms of abnormal impulse formation.

Notes: Flunarizine and Ryanodine in Acquired TdP. Introduction: Ryanodine, a specific blocker of the Ca2+ release channel of the sarcoplasmic reticulum, and flunarizine, a[Ca2+], overload blocker, possess antiarrhythmic effects against delayed after depolarizations (DADs) and DAD-dependent arrhythmias. In vitro controversy exists about their effect on early after depolarizations (EADs): no effect was reported on cesium-induced EADs, while ryanodine did prevent EADs induced by isoproterenol. To study the possible role of intracellular Ca2+ overload in acquired EAD-dependent torsades de pointes (TdP) arrhythmias, we tested the effects of flunarizine and ryanodine in our animal model of TdP. Methods and Results: Anaesthetized dogs with chronic AV block received d-sotalol or almokalant followed by pacing. A subset of dogs with reproducible TdP (≥ 3 times) were selected to receive flunarizine (2 mg/kg per 2 min) or ryanodine (10 μg/kg per 10 min). After dsotalol, TdP was induced at a mean cycle length of the idioventricular rhythm (CL-IVR) of 2070 ± 635 msec and a QT(U) interval of 535 ± 65 msec. Induction of TdP was prevented by flunarizine in all experiments (8/8): electrophysiologically this was associated with a decrease in CL-IVR, QT(U), and QTc interval (390 ± 100 to 320 ± 45, P 〈 0.05). Ryanodine prevented TdP induction in 4 of 5 experiments and decreased the CL-IVR, QT(U), and the QTc interval from 385 ± 75 to 320 ± 20 msec (P 〈 0.05). Both drugs also suppressed the almokalant-induced EADs and related ectopic activity. This antiarrhythmic action corresponded with the inability to reinduce TdP by pacing. Conclusions: Blockade of the Ca2+ release channel of the sarcoplasmic reticulum by ryanodine or the reduction of [Ca2+] overload by flunarizine prevents induction of EAD-dependent acquired TdP arrhythmias, suggesting a role for [Ca2+]i overload in acquired TdP.

Notes: Cryoablation of the Proximal AV Node. Introduction: Radiofrequency (RF) is the most commonly used energy source for the treatment of cardiac arrhythmias. Surgical experience has shown that cryoablation also is effective for ablating arrhythmias. The aims of this study were to (I) investigate the feasibility of inducing permanent complete AV block (CAVB). (2) investigate the value of cold mapping to select the cryoablation site to produce permanent CAVB, (3) study the macro- and microscopic lesion characteristics 6 weeks later, and (4) compare them to those produced with RF energy. Methods and Results: A new steerable 8.5-French bipolar electrode catheter having a thermocouple with a 3-mm tip using N2O as the refrigerant controlled by a cryoconsole was used. Six mongrel dogs were anesthetized, and the catheter was positioned via the femoral vein across the tricuspid valve to record a large low right atrial and a small His-bundle potential. After cold mapping (-15° to -20°C tip temperature) resulted in ECG modifications, cryothermia (-70°C) was given twice, lasting 5 minutes each, to create permanent CAVB (Cryo group). Additionally, RF catheter ablation of the AV node was performed in two anesthetized mongrel dogs (RF group). In the Cryo group, a permanent proximal CAVB was created in four dogs (block occurred within 10 to 20 sec of cryothermia). Permanent right bundle branch block was obtained in one dog and transient CAVB in the remaining dog. In both dogs of the RF group, permanent CAVB was obtained. The cryolesions consisted of well-circumscribed, homogeneous areas of fibrotic tissue without viable cardiomyocytes. Lesions produced with RF were less circumscribed and inhomogeneous, with clear evidence of viable cardiomyocytes and cartilage formation (patchy lesions). Conclusions: (1) Permanent CAVB can he created by using a steerable cryoablation catheter. (2) Histologically, cryoablated sites were homogeneous and showed fibrotic tissue without signs of chronic inflammation and no evidence of viable myocytes. (3) Lesions created with RF were less homogenous and still contained viable myocytes within the lesion and cartilage formation. (4) The arrhythmogenic significance of these differences requires further study. (5) The technology of using reversible cold mapping has the potential to identify the successful ablation site and warrants further clinical study.