Notes: We investigated the electrophysiological actions of dofetilide upon the ventricular myocardium to determine whether the drug modifies the inhibitory effects of subthreshold stimuli trains upon ventricular refractoriness. In nine Langendorff perfused rabbit hearts, ventricular epicardial electrodes were used to determine the following parameters at baseline and during dofetilide perfusion (0.5 micromolar): effective (ERP) and functional (FRP) refractory periods, conduction velocity (CV), wavelength (WL), and ERP prolongation (inhibitory effect) induced by subthreshold stimuli trains (STr) at pulse frequencies of 100, 300, and 600 Hz. Dofetilide significantly prolongs ventricular refractoriness and WL: ERP increment (Dofetilide-baseline, 300 ms cycle length) = 33 ± 20 ms (24 ± 12%, P 〈 0.01); FRP increment = 37 ± 19 ms (23%± 10%, P 〈 0.01); WL increment = 4.1 ± 3.2 cm (27%± 20%, P 〈 0.01), without modifying CV. These effects are diminished upon increasing the stimulation frequency: ERP increment (Dofetilide-baseline, 150 ms cycle length) = 18 ± 10 ms (18%± 12%, P 〈 0.05); FRP increment = 15 ± 4 ms (14%± 5%, P 〈 0.01); WL increment = 1.9 ± 1.7 cm (18%± 10%, P 〈 0.01). The STr significantly prolong ERP, and the increments obtained at baseline and during dofetilide perfusion are similar. In both cases the inhibitory effect is slight for STr of 100 Hz (baseline = 5 ± 3 ms, dofetilide = 6 ± 5 ms, with nonsignificant (ns) differences between them) and highly manifest for STr of 300 Hz (baseline = 76 ± 33 ms, dofetilide = 87 ± 32 ms, ns) and 600 Hz (baseline = 109 ± 39 ms, dofetilide = 89 ± 34 ms, ns). Dofetilide prolongs ventricular refractoriness and WL, exerting a reverse-frequency dependent effect without modifying CV. The inhibitory effect of STr is greater when their pulse frequency is increased, and its magnitude is similar under the influence of dofetilide. During dofetilide perfusion the inhibitory effect of STr adds to the ERP prolongation induced by the drug. (PACE 2004; 27:327–332)

Notes: Electrical cardioversion is the most effective and safe method to restore sinus rhythm in patients with persistent AF. However, at least 25% of electrical cardioversions are unsuccessful. The aim of the present study was to evaluate, in a prospective, randomized and double-blind study, the efficacy of a pretreatment with intravenous flecainide in patients who underwent electrical cardioversion. Fifty-four consecutive patients with persistent AF, mean arrhythmia duration 8 (mean 3–18) weeks, were randomized in two groups. In the first group (n = 26), patients received flecainide (2 mg/kg as a 30-minute IV infusion) before electrical cardioversion. In the second group (n = 28), 100 mL IV infusion of 5% glucose was administered 30 minutes before electrical cardioversion. The study evaluated the (1) acute efficacy of electrical cardioversion, (2) mean and maximal energy required, (3) mean number of shocks needed, and (4) incidence of complications. The two groups were similar in terms of age, sex, mean AF duration, left ventricular systolic function, atrial dimension, and cardiovascular risk factors. Seventy-seven percent of patients recovered sinus rhythm with electrical cardioversion. No statistical difference was noted between the two groups: flecainide 19/26 (73%) versus placebo 23/28 (82%). No significant differences were found concerning mean or maximal energy and number of shocks required. No major complications were observed. After a 30-day follow-up, 54% of patients maintained sinus rhythm with no difference between the two groups. Pretreatment with intravenous flecainide before electrical cardioversion is not useful in reducing technical failure of cardioversion, however, flecainide does not diminish the effectiveness of electrical cardioversion. (PACE 2004; 27:368–372)

Notes: CHORRO, F.J., et al.: Mapping of Atrial Activation Patterns After Inducing Contiguous Radiofrequency Lesions: An Experimental Study. High resolution mapping techniques are used to analyze the changes in atrial activation patterns produced by contiguous RF induced lesions. In 12 Langendorff-perfused rabbit hearts, left atrial activation maps were obtained before and after RF induction of epicardial lesions following a triple-phase sequential protocol: (phase 1) three separate lesions positioned vertically in the central zone of the left atrial wall; (phase 2) the addition of two lesions located between the central lesion and the upper and lower lesions; and (phase 3) the placement of four additional lesions between those induced in the previous phases. In six additional experiments a pathological analysis of the individual RF lesions was performed. In phase 1 (lesion diameter = 2.8 ± 0.2 mm, gap between lesions = 3 ± 0.8 mm), the activation process bordered the lesions line in two (2.0-ms cycles) and four experiments (1.0-ms cycles). In phase 2, activation bordered the lesions line in eight (2.0-ms cycles, P 〈 0.01 vs control) and nine experiments (1.0-ms cycles, P 〈 0.001), and in phase 3 this occurred in all experiments except one (both cycles, P 〈 0.001 vs control). In the experiments with conduction block, the increment of the interval between activation times proximal and distal to the lesions showed a significant correlation to the length of the lesions (r = 0.68, P 〈 0.05, 100-ms cycle). In two (17%) experiments, sustained regular tachycardias were induced with reentrant activation patterns around the lesions line. In conclusion, in this acute model, atrial RF lesions with intact tissue gaps of 3 mm between them interrupt conduction occasionally, and conduction block may be frequency dependent. Lesion overlap is required to achieve complete conduction block lines. Tachycardias with reentrant activation patterns around a lesions line may be induced.

Notes: An analysis was made in 14 isolated and perfused rabbit hearts of the electrophysiological effects of selective radiofrequency (RF) delivery in the anterior (group I, n = 7) or posterior zone (group II, n = 7) of the Koch triangle, with the aim of modifying atrioventricular nodal (AVN) conduction without suppressing 1:1 transmission. After opening the right atrium, RF was delivered (0.5 W) with a 1-mm diameter unipolar electrode positioned in the selected zone until a prolongation of no less than 15% was obtained in the Wenckebach cycle length (WCL). Before and after (30 min) RF, anterograde and retrograde AVN refractoriness and conduction were evaluated, stimulating from the crista terminalis (CT), the interatrial septum (IAS), and from the RV epicardium. After RF, the fallowing percentage increments were observed in group I: AH(CT) = 36%± 9%, AH(IAS) = 38%± 11%, WCL(CT) = 28%± 8%, WCUIAS) = 22%± 6%. functional refractory period (FRP) of the AVN(CT) = 13%±11%, FRP-AVN(IAS) = 13%± 8%, retrograde WCL = 20%±19%. and retrograde FRPVA = 13%± 16%. The increments observed in group II and the significances of the differences with respect to group I were: AH(CT) = 11%± 14% (P 〈 0.01), AH(IAS) = 19%± 32% (NS), WCL(CT) = 42%± 14% (P 〈 0.05), WCL(IAS) = 42%± 16% (P〈0.01), FRP-AVN(CT) = 28%± 28% (NS). FRP-AVN(IAS) = 21 %± 19% (NS), retrograde WCL = 35%± 24% (NS), and retrograde FRP = 16%± 13% (NS). In both groups, the AH interval variations were not correlated with those of the rest of the parameters analyzed. Truncated nodal function curves suggestive of a dual A V nodal path way were obtained in three experiments, though in only one of them was this observed under basal conditions. In the other two experiments with dual AV nodal physiology only after RF (one from each group), AV nodal reentrant tachycardias were triggered with atrial extrastimulus at coupling intervals equal to or shorter than at those that cause a sudden lengthening of the AH interval. RF delivered in the anterior and posterior zones of the Koch triangle produced effects of different magnitude on the AH interval and Wenckebach cycle length. In the anterior zone the AH interval was prolonged to a greater extent, while in the posterior zone the effects were greater on the Wenckebach cycle length. No correlation existed between the variations in AH interval and Wenckebach cycle length, regardless of where RF was delivered. The evaluation of anterograde AV nodal refractoriness was similar when stimulating from the crista terminalis or from the interatrial septum. By delivering RF, it was possible to induce dual AV nodal physiology and reentrant tachycardias. (PACE 1997; 20[Pt. I]:1261-1273]

Notes: CHORRO, F.J., et al.: Opposite Effects of Myocardial Stretch And Verapamil on The Complexity of The Ventricular Fibrillatory Pattern: An Experimental Study. An experimental model is used to analyze the effects of ventricular stretching and verapamil on the activation patterns during VF. Ten Langendorff-perfused rabbit hearts were used to record VF activity with an epicardial multiple electrode before, during, and after stretching with an intraventricular balloon, under both control conditions and during verapamil (Vp) infusion (0.4–0.8 μmol). The analyzed parameters were dominant frequency (FrD) spectral analysis, the median (MN) of the VF intervals, and the type of activation maps during VF (I = one wavelet without block lines, II = two simultaneous wavelets with block lines, III = three or more wavelets with block lines). Stretch accelerates VF (FrD: 22.8 ± 6.4 vs 15.2 ± 1.0 Hz, P 〈 0.01; MN: 48 ± 13 vs 68 ± 6 ms, P 〈 0.01). On fitting the FrD time changes to an exponential model after applying and suppressing stretch, the time constants (stretch: 101.2 ± 19.6 s; stretch suppression: 97.8 ± 33.2 s) do not differ significantly. Stretching induces a significant variation in the complexity of the VF activation maps with type III increments and type I and II decrements (control: I = 17.5%, II = 50.5%, III = 32%; stretch: I = 7%, II = 36.5%, III = 56.5%, P 〈 0.001). Vp accelerates VF (FrD: 20.9 ± 1.9 Hz, P 〈 0.001 vs control; MN: 50 ± 5 ms, P 〈 0.001 vs control) and diminishes activation maps complexity (I = 25.5%, II = 60.5%, III = 14%, P 〈 0.001 vs control). On applying stretch during Vp perfusion, the fibrillatory process is not accelerated to any greater degree. However, type I and II map decrements and type III increments are recorded, though reaching percentages similar to control (I = 16.5%, II = 53%, III = 30.5%, NS vs control). The following conclusions were found: (1) myocardial stretching accelerates VF and increases the complexity of the VF activation pattern; (2) time changes in the FrD of VF during and upon suppressing stretch fit an exponential model with similar time constants; and (3) although stretching and verapamil accelerate the VF process, they exert opposite effects upon the complexity of the fibrillatory pattern.

Notes: Mapping techniques are used to study the significance of the morphological patterns of the electrograms (EGMs) obtained during VF in an experimental model. In 24 isolated rabbit heart preparations recordings were made of activation during VF using a multiple electrode (121 unipolar electrodes) positioned on the lateral wall of the left ventricle. Three types of activation maps were selected: (A) with functional block of an activation front; (B) with epicardial breakthrough; and (C) with a single broad wavefront without block lines. The EGMs were classified as negative (Q), positive-negative with a predominance of the negative (rS) or positive wave (Rs), and positive (R). In 60 type A maps the morphology in the zone limiting the block line corresponded to an R wave in 55 (92%) cases and to Rs in 5 (8%) cases. In 67 type B maps, the EGM in the earliest activation zone most often showed Q wave morphology (48 [72%] cases), followed by rS (18 [27%] cases), and Rs morphology (1 [1%] case); in no case was R wave morphology seen. Finally, in 78 type C maps the morphology corresponded to a Q wave in 15 (19%) cases, rS in 38 (49%), Rs in 24 (31%), and R in a 1 (1%) case. The differences between the three types of maps were significant (P 〈 0.0001). Q wave EGM sensitivity for indicating the existence of an epicardial breakthrough pattern was 72%, with a specificity of 89%, and positive and negative predictive values of 76% and 87%, respectively. R wave EGM sensitivity for indicating the existence of conduction block was 92%, with a specificity of 99%, and positive and negative predictive values of 98% and 97%, respectively. R wave morphology is highly sensitive and specific for indicating conduction block. EGM recordings with initial positivity predominance are infrequent in the earliest activation zones of epicardial breakthrough during VF. The recording of the EGM with Q wave morphology indicates centrifugal activation from the explored zone. (PACE 2003; 26:1262–1269)

Notes: The characteristics of ventricular fibrillatory signals vary as a function of the time elapsed from the onset of arrhythmia and the maneuvers used to maintain coronary perfusion. The dominant frequency (FrD) of the power spectrum of ventricular fibrillation (VF) is known to decrease after interrupting coronary perfusion, though the corresponding recovery process upon reestablishing coronary flow has not been quantified to date. With the aim of investigating the recovery of the FrD during reperfusion after a brief ischemic, period, 11 isolated and perfused rabbit heart preparations were used to analyze the signals obtained with three unipolar epicardial electrodes (E1-E3) and a bipolar electrode immersed in the thermostatizfid organ bath (E4), following the electrical induction of VF. Recordings were made under conditions of maintained coronary perfusion (5 min), upon interrupting perfusion (15 mini, and after reperfusion (5 min), FrD was determined using Welch's method. The variations in FrD were quantified during both ischemia and reperfusion, based on an exponential model AFrD = A exp (-t/C). During ischemia ΔFrD is the difference between FrD and the minimum value, while t is the time elapsed from the interruption of coronary perfusion. During reperfusion ΔFrD is the difference between the maximum value and FrD, while t is the time elapsed from the restoration of perfusion, A is one of the constants of the model, and C is the time constant. FrD exhibited respective initial values of 16.20 ± 1.67, 16.03 ± 1.38, and 16.03 ± 1.80 Hz in the epicardial leads, and 15.09 ±1.07 Hz in the bipolar lead within the bath. No significant variations were observed during maintained coronary perfusion. The fit of the FrD variations to the model during ischemia and reperfusion proved significant in nine experiments. The mean time constants C obtained on fitting to the model during ischemia were as follows: El =294.4 ± 75.6, E2 = 225.7 ± 48.5, E3 = 327.4 ± 79.7, and E4 = 298.7 ± 43.9 seconds. The mean values of C obtained during reperfusion, and the significance of the differences with respect to the ischemic period were: El = 57.5 ± 8.4 (P ± 0.01), E2 = 64.5 ± 11.2 (P0.01), E3 = 80.7 ± 13.3 (P 〈 0.01), and E4 = 74.9 ± 13.6 (P 〈 0.0001). The time course variations of the FrD of the VF power spectrum fit an exponential model during ischemia and reperfusion. The time constants of the model during reperfusion after a brief ischemic period are significantly shorter than those obtained during ischemia.

Notes: The electrophysiological effects of RF ablation upon the areas in proximity to the lesioned zones have not yet been well characterized. An experimental model is used to investigate atrial conduction in the boundaries of RF damaged zones. In 11 isolated and perfused rabbit hearts, endocardial atrial electrograms were recorded using an 80-Iead multiple electrode positioned in the left atrium. Both before and after the RF application (5 W, 8 s, 1-mm diameter unipolar epicardial electrode) in the mid-portion of the free left atrial wall, measurements were made of conduction time from the pacing zone (posterior wall of the left atrium) to three points between 7.5 and 7.9 mm distal to the damaged zone. Conduction velocity and the direction of the activation propagation vector were determined in ten groups of four electrodes positioned around the damaged zone, and at the left atrial appendage. The mean diameter (± SEM) of the transmural lesions produced by RF ablation and defined by macroscopic examination was 4.2 ± 0.2 mm. The conduction times to the three points distal to the lesion site were significantly prolonged as a result of RF ablation: 7.6 ± 0.4, 7.4 ± 0.5, and 6.9 ± 1.0 ms (control); and 11.3 ± 1.0 (P ≤ 0.01), 11.1 ± 1.3 (P 〈 0.01), 10.6 ± 1.4 ms (P 〈 0.05) (post-RF). The differences between the conduction velocities determined in the areas surrounding the lesion, before and after RF application, failed to reach statistical significance: 86.2 ± 6.5 cm/s (control) versus 75.5 ± 5.7 cm/s (post-RF) (NS). After RF, significant variations were only observed in the direction of impulse propagation in the proximal-inferior quadrant adjacent to the lesion site, the difference being -61°± 18° (P 〈 0.02). In 2 of 4 experiments in which the lesion size was increased by a second RF application (5 W, 16 s), tachycardias with activation sequence around the lesion could be induced, with cycle lengths of 56 and 50 ms, respectively. In the atrial wall, the conduction times to the regions distal to the RF lesion are significantly prolonged. No significant changes are observed in conduction velocity in the areas in proximity to the lesion. Prolonged conduction to the areas distal to the ablation site is due to the lengthened pathway traveled by the impulses in reaching these areas. Tachycardias with activation patterns that suggest reentry around the RF damaged zone may be induced.

Notes: A study is made of the characteristics of the atrial potentials recorded in the Koch triangle and its proximity, their variations on modifying the site of cardiac pacing, and their usefulness as markers of a distinct zone of the AV junction. In 12 isolated and perfused rabbit heart preparations an analysis was made of the endocardial atrial electrograms recorded with a multiple electrode positioned in the AV junction. The electrograms were obtained during spontaneous rhythm and on pacing at the crista terminalis (CT), interatrial septum (IAS), left atrium, and right ventricle. Double potentials were frequently obtained. On pacing at the CT, high-low double potentials (DP [H-L]) were more frequent (P 〈 0.05) in the low CT (11%± 4% of the electrodes) and posterior zone of the Koch triangle (6%± 5%), than in the IAS (1 %± 2%) and anterior zone of the Koch triangle (2%± 3%). A similar tendency was observed either on pacing at the left atrium or during spontaneous rhythm. During pacing at the IAS the percentages of low-high double potentials (DP[L-H]) were significantly higher (P 〈 0.05) in the low CT (7%± 6%). DP (H-L) were of low sensitivity in indicating a given zone; maximum sensitivity was 61 % in the low CT when pacing at the CT. DP (L-H) proved even less seusitive in indicating a given zone, though their specificity was greater in the low CT (91%) during pacing at the IAS. The specific zones in which the highest percentages of DP (H-L) or DP (L-H) are obtained depend on the site of cardiac pacing. On pacing at the IAS. DP (L-H) are more specific of the low CT. During pacing at both the CT and at the IAS. DP (H-L) sensitivity in indicating a given zone is low.

Notes: Introduction: We hypothesize that local modifications in electrophysiological properties, when confined to zones of limited extent, induce few changes in the global activation process during ventricular fibrillation (VF). To test this hypothesis, we produced local electrophysiological modifications by stretching a circumscribed zone of the left ventricular wall in an experimental model of VF. Methods and Results: In 23 Langendorff-perfused rabbit hearts frequency, time–frequency and time-domain techniques were used to analyze the VF recordings obtained with two epicardial multiple electrodes before, during, and after local stretching produced with a left intraventricular device. Acute local stretching accelerated VF in the stretched zone reversibly and to a variable degree, depending on the magnitude of stretch and the time elapsed from its application. In the half time (5 minutes) of the analyzed period, a longitudinal lengthening of 12.1 ± 4.5% (vertical axis) and 11.8 ± 6.2% (horizontal axis) in the stretched zone produced an increase in the dominant frequency (DFr) (15.2 ± 1.9 versus 18.8 ± 2.5 Hz, P 〈 0.0001), a decrease in mean VV interval (63 ± 8 versus 53 ± 6 msec, P 〈 0.001), and an increase in the complexity of the activation maps—with more areas of conduction block and more breakthrough patterns (23% versus 37%, P 〈 0.01), without significant changes in the percentages of complete reentry patterns (9% versus 9%, ns). Simultaneously, in the nonstretched zone, no variations were observed in the DFr (15.2 ± 2.1 versus 15.3 ± 2.5 Hz, ns), mean VV intervals (66 ± 8 versus 65 ± 8 msec, ns), or types and percentages of maps with breakthrough (25% versus 20%, ns) or reentry patterns (12% versus 8%, ns). No significant correlation was observed between the DFr in the two zones (R = 0.24, P = 0.40). Conclusion: Local stretching increases the electrophysiological heterogeneity of myocardium and accelerates and increases the complexity of VF in the stretched area, without significantly modifying the occurrences of the types of VF activation patterns in the nonstretched zone.