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Studies have shown that long-term vagal stimulation is protective against ventricular fibrillation; however, the effects of acute vagal stimulation during ventricular fibrillation in the normal heart have not been investigated. We examined the effects of acute vagal stimulation on ventricular fibrillation in a canine model. In 4 dogs, we induced 30-second periods of ventricular fibrillation by means of intraventricular pacing. During 2 of the 4 periods of fibrillation that we analyzed, vagal stimulation was delivered through electrodes in the caudal ends of the vagus nerves. Noncontact unipolar electrograms were recorded from 3 ventricular regions: the basal septum, apical septum, and lateral free wall. We then computed the most frequent cycle length, mean organization index, and mean electrogram amplitude for each region. During fibrillation, vagal stimulation shortened the most frequent cycle lengths in the basal septum (P=0.02) and apical septum (P=0.0001), but not in the lateral wall (P=0.46). In addition, vagal stimulation significantly reduced the mean organization indices in the apical septum (P <0.001) and lateral wall (P <0.001), but not in the basal septum (P=0.19). Furthermore, vagal stimulation raised the mean electrogram amplitude in the basal septum (P <0.01) but lowered it substantially in the apical septum (P=0.00005) and lateral wall (P=0.00003). We conclude that vagal stimulation acutely affects the characteristics of ventricular fibrillation in canine myocardium in a spatially heterogeneous manner. This nonuniformity of response may have implications with regard to manipulating the autonomic system as a means of modifying the substrate for ventricular dysrhythmias. [ABSTRACT FROM AUTHOR]

Introduction: Assessment of ventricular activation pattern is critical to the successful ablation of ventricular tachycardia (VT). We have previously shown that the global atrial activation pattern during tachycardia can be rapidly and accurately assessed by calculating the postpacing interval variability (PPIV); PPIV was minimal in circuitous tachycardias and highly variable in centrifugal tachycardias. In the present study, we use the PPIV to determine the ventricular global activation pattern during VT. Methods: Patients with mappable VT were included. We defined global ventricular activation as either centrifugal (arising from a focus with radial expansion) or circuitous (gross macro-reentrant circuit), based on the findings of electroanatomic mapping. PPIV was calculated as the difference in postpacing interval with right ventricular apical overdrive pacing during tachycardia at cycle lengths (CL) 10 ms and 30-ms shorter than tachycardia, regardless of the origin of the tachycardia. We studied 20 patients with 23 VTs (11 centrifugal, mean CL 390 ± 36.1 ms; 12 circuitous, mean CL 418 ± 75.7 ms). Results: The mean PPIV was 45 ± 16 ms for patients with centrifugal VT and 6.7 ± 4.1 ms for patients with circuitous VT. Rank sum analysis of PPIV showed a significant difference between the two groups (P < 0.05). Conclusions: Our data suggest that the global ventricular activation pattern during VT can be rapidly and accurately defined by assessing the PPIV. This technique allows for a rapid confirmation of the tachycardia activation and significantly facilitates mapping and ablation. (PACE 2010; 33:129–134) [ABSTRACT FROM AUTHOR]

Mutations of SCN5A, gene-encoding α-subunit of cardiac sodium channel, can cause mixed phenotypes of Brugada syndrome (BrS) and cardiac conduction diseases (CCD). We have identified a nucleotide change of SCN5A (4178T > G), which results in a nonsense mutation, L1393X, in a 36-year-old Caucasian man who presented with intraventricular conduction delays and BrS-type electrocardiogram change. To study biophysical characteristics of L1393X-SCN5A, electrophysiological and immuno-staining studies were performed using mammalian expression systems. While WT-SCN5A showed significant currents (93.3 ± 10.6 pA/pF; 1 μg plasmid), L1393X (5 μg) did not generate any significant currents in NIH-3T3 cells. The cells cotransfected with WT (0.5 μg) and L1393X (0.5 μg) showed approximately 50% current amplitudes compared to the WT (1 μg). Voltage dependency of a steady-state activation and inactivation was not affected by the cotransfection of L1393X. Immuno-histochemical stainings demonstrated that L1393X proteins were expressed in the plasma membranes. Our study demonstrated that L1393X-SCN5A does not form functional channel proteins, which might account for the patient's mixed phenotypes of BrS and CCD. [ABSTRACT FROM AUTHOR]

Introduction: Knowledge of the global atrial activation pattern is critical to ablation of an atrial arrhythmia. We hypothesized that the variability in post-pacing intervals (PPIs) with pacing at different cycle lengths (CLs) from the same pacing site, regardless of distance to the circuit, can be used to identify atrial activation patterns during tachycardia. Methods and Results: Consecutive patients referred for ablation of organized atrial arrhythmias were included (n = 28, 31 total tachycardias). The variability in PPIs (PPIV) was calculated by comparing the difference in PPIs after overdrive pacing with 5-second trains 10, 20, and 30 ms shorter than the tachycardia cycle length (TCL). The global activation pattern was defined as circuitous (macroreentrant atrial circuit) or centrifugal (focal origin with centrifugal radiation) by electroanatomic mapping. Except for one case, all pacing was performed from the proximal coronary sinus bipole. Circuitous tachycardias (n = 17, all macro-reentrant) exhibited minimal variability with pacing at 10 ms and 30 ms shorter than TCL (6.0 ± 2.5 ms), whereas centrifugal tachycardias (n = 14, 8 microreentrant) displayed a high degree of variability (56.5 ± 20.6 ms). Rank sum analysis of PPIV suggests that the two groups are indeed distinct (P < 0.001). Using PPIV cutoffs of ≤10 ms and ≥30 ms, circuitous and centrifugal activation patterns could be distinguished with a high degree of sensitivity (94% circuitous, 92.8% centrifugal) and 100% specificity. Conclusions: Our data support the use of PPIV to rapidly and accurately predict the global activation pattern during atrial arrhythmia. [ABSTRACT FROM AUTHOR]