We studied whether repetitive intracardiac shock discharges of implantable cardioverter defibrillators (ICDs) provoke an enduring enhancement of startle responses.The study population comprised 134 patients with an ICD. Among those, 67 patients had experienced shock delivery. Thirty-five patients had received five or more shocks. We used the startle reflex paradigm, which consisted of 15 acoustic stimuli (95 dB, 1000 Hz, 500 ms duration). Skin conductance response was measured using a constant 0.5 V through 8-mm electrodes placed on each subject's nondominant palm. Response magnitude was calculated by subtracting the baseline response level of the 2 seconds immediately preceding tone onset from the maximum response level within 1 to 4 seconds after tone onset. The left orbicularis oculi electromyogram (EMG) response was calculated by subtracting the mean EMG level during the 2 seconds immediately preceding tone onset from the highest EMG level measured within 40 to 200 ms after tone onset. Habituation was defined by the response slope of the regression equation and by the number of trials required to reach the nonresponse criterion.Although EMG response measures of magnitude and habituation failed to yield differences between study groups, patients who had experienced five or more ICD shocks exhibited a significantly larger skin conductance response magnitude in comparison to the patients who had experienced fewer than five shocks (median, interquartile range: 0.364, 0.209-0.618 vs. 0.512, 0.375-0.791; Mann-Whitney U test, p =.007). Poorer habituation in the group with five or more shocks in comparison with the low shock group was confirmed both by the number of trials needed to reach the nonresponse criterion (median, interquartile range: 10, 5-14 vs. 5, 2-13; p =.003) and by the response slope (median, interquartile range: 0.209, 0.116-0.274 vs. 0.262, 0.181-0.332; p =.008). After controlling for potential confounding factors (age, anxiety, aversiveness of stimuli, time since last shock experience, and use of beta-adrenoceptor antagonists), intracardiac shock discharges had the strongest impact on augmented skin conductance response magnitude (adjusted odds ratio = 3.0, 95% confidence interval = 1.3-7.2, p =.01) and impaired habituation (adjusted odds ratio = 2.8, 95% confidence interval = 1.2-6.3; p =.015).Intracardiac shock discharges are associated with augmented skin conductance responses and slower habituation, indicating sustained sympathetic arousability, which is presumably centrally mediated.
We investigated how modulation of L-type calcium current affects the class III antiarrhythmic effect of dofetilide. Action-potential duration (APD) was determined in guinea pig papillary muscle by microelectrode techniques at different stimulation frequencies (0.5-3 Hz). The APD-prolonging effect (ΔAPD) of 10 nM dofetilide was reversed frequency dependent; it was 51 ± 6 ms at 0.5 Hz and lower at 3 Hz, 21 ± 3 ms. Either 10 μM diltiazem or 0.1 μM Bay K 8644 (BayK) was added to decrease or increase L-type calcium currents. In the presence of dofetilide + diltiazem, ΔAPD was reduced to 32 ± 4 ms at 0.5 Hz but not affected at 3 Hz. Conversely, dofetilide + BayK further prolonged ΔAPD to 78 ± 10 ms at 0.5 Hz but not at 3 Hz. When 10 μM dihydroouabain, a digitalis glucoside, was added to dofetilide, ΔAPD was more pronounced at 0.5 Hz and reduced at 3 Hz. We conclude that the reversed frequency-dependent effect of dofetilide on APD can be modulated by altering L-type calcium currents. With reduced calcium current, the frequency profile is less reversed and more favorable. The similarity of BayK and dihydroouabain in aggravating the reversed frequency-dependent effect of dofetilide is in line with a contribution of intracellular calcium to this reversed rate-dependent profile in the guinea pig ventricle.
Radiofrequency catheter ablation (RFCA) is an effective treatment for the interruption of accessory bypass tracts in WPW syndrome or the modification of the AV-nodal conduction system in patients with AV-nodal tachycardias. However RFCA may also damage cardiac innervation. The purpose of this pilot study was to assess possible changes in sympathetic innervation after RFCA as evaluated by the cathecholamine analog carbon-11-hydoxyephedrine (HED) positron emission tomography (PET) which allows the visualisation of sympathetic nerve terminals. We investigated nine patients with supraventricular tachycardias before and two to six weeks after RFCA. Myocardial perfusion was depicted by n-13-ammonia-PET. In addition to visual analysis, HED retention was quantified in the myocardial quadrant distal to the location of intervention; these results were compared with values in remote areas. Before RFCA, myocardial perfusion showed homogenous distribution in 8 of 9 patients. One patient showed a perfusion defect in the posterior wall. HED retention matched perfusion distribution in all patients. After RFCA there was no significant change observed either in ammonia or in HED distribution. Quantitative HED retention data showed no significant change before versus after RFCA. Thus, HED-PET does not demonstrate any abnormalities of tracer uptake indicating integrity of sympathetic nerve terminals after radiofrequency ablation therapy.
SCHREIECK, J., et al. : Radiofrequency Ablation of Cardiac Arrhythmias Using a Three‐Dimensional Real‐Time Position Management and Mapping System. . A recently developed three‐dimensional real‐time position management system (RPM) uses an ultrasound ranging technique that enables multiple distance measurements between two reference catheters and a mapping catheter each equipped with ultrasound transducers. In addition to three‐dimensional representation of the catheters and ablation sites it displays real‐time movements of catheters (including the tip and shaft). A recently released version of the system enables additional geometry reconstruction of the heart chamber and activation mapping. This study included 21 patients (mean age 59 ±14.5 years) referred for radiofrequency catheter ablation of various arrhythmias. Geometry was reconstructed by tracing the endocardial contour of the respective heart chambers. Global and local color coded activation maps were constructed to confirm the nature of arrhythmia and to guide ablation. Spontaneous or induced arrhythmias were typical atrial flutter ( n = 8 ), atypical atrial flutter ( n = 3 ), atrioventricular nodal reentrant tachycardia ( n = 3 ), atrial tachycardia ( n = 2 ), atrial fibrillation ( n = 2 ), ventricular tachycardia ( n = 2 ), and Wolff‐Parkinson‐White syndrome ( n = 1 ). Geometry reconstruction and mapping of arrhythmias were possible in 20 of 21 patients. RPM‐guided radiofrequency ablation was successful in 19 (95%) of 20 patients. Due to difficulties in steering the RPM mapping/ablation catheter, in 6 (28%) successfully mapped patients, radiofrequency ablation was performed using another catheter. In one patient, the RPM‐guided map was inconclusive and in another patient, ablation failed due to multiple reentrant circuits. No complications were observed. In conclusion, the new RPM system enables geometry reconstruction and three‐dimensional positioning of the ablation catheters, reconstruction of the activation maps, marking of anatomic structures and reproducible tracking of multiple ablation sites. The system could be used to guide radiofrequency ablation of atrial and ventricular arrhythmias.