Role of the posterior papillary muscle and purkinje potentials in the mechanism of ventricular fibrillation in open chest dogs and Swine: effects of catheter ablation

BACKGROUND: Papillary muscle (PM) ablation may terminate ventricular fibrillation (VF) in rabbit hearts. Whether or not PM ablation prevents ventricular fibrillation (VF) induction in large animals is unknown. METHODS: We performed noncontact endocardial mapping and/or high-density epicardial mapping during VF in 12 dogs and 16 swine and tested the effects of posterior PM (PPM) ablation on VF inducibility. RESULTS: During VF in progressive global ischemia (3 swine and 2 dogs), the highest dominant frequency (DF) was near PPM. The majority of the reentrant wavefronts during a propranolol infusion (swine) were anchored to the PPM. Purkinje potentials onset were recorded on the PPM both during sinus rhythm and during VF. Radiofrequency (RF) ablation of the endocardium on the PPM with a linear extension of the ablation line from the PPM to the mitral valve annulus and then the left ventricular apex in 7 dogs reduced the VF inducibility from 100% at baseline to 22% after ablation (P < 0.0001). RF applications to the anterolateral wall of dogs (n = 3) did not prevent VF induction. The application of RF energy near the PPM frequently initiated VF in swine (n = 7), preventing subsequent testing of VF inducibility. CONCLUSION: In dogs and swine, the highest DF and majority of reentrant wavefronts during VF with acute global ischemia or during a propranolol infusion were located on the PPM. RF ablation targeted at the PPM reduced the inducibility of VF in normal dogs. However, the same ablation provoked incessant VF in swine, preventing subsequent testing of VF inducibility.     

I(Ks) block by HMR 1556 lowers ventricular defibrillation threshold and reverses the repolarization shortening by isoproterenol without rate-dependence in rabbits

Introduction: The slow delayed rectifier K⁺ current (I_Ks) contributes little to ventricular repolarization at rest. It is unclear whether I_Ks plays a role during ventricular fibrillation (VF) or ventricular repolarization at rapid rates during β-adrenergic stimulation.
Methods and Results: In an in vivo rabbit model, we evaluated the effects of HMR 1556 (1 mg Kg⁻¹+ 1 mg kg ⁻¹ hr ⁻¹ i.v.), a selective I_Ks blocker, on monophasic action potential duration at 90% repolarization (MAPD₉₀), ventricular effective refractory period (VERP), and defibrillation threshold (DFT). In perfused rabbit hearts, the effects of HMR 1556 (10 and 100 nM) in the presence of isoproterenol (5 nM) on MAPD₉₀ and VERP were studied at cycle lengths (CLs) 200–500 msec. In vivo , HMR 1556 prolonged MAPD₉₀ by 6 ± 1 msec at CL 200 msec (P < 0.01, n = 6), lowered DFT from 558 ± 46 V to 417 ± 31 V (P < 0.01), and decreased the coefficient of variation in the VF inter-beat deflection intervals from 8.9 ± 0.6% to 6.5 ± 0.4% (P < 0.05) compared with control. In perfused rabbit hearts, isoproterenol shortened MAPD₉₀ by 5 ± 1 msec at CL 200 msec and 11 ± 4 msec at CL 500 msec (P < 0.05, n = 7). This shortening was reversed by HMR 1556 (P < 0.05), and both effects were rate-independent.
Conclusion: I_Ks block increases VF temporal organization and lowers DFT, and I_Ks that is activated following β-adrenergic stimulation contributes to ventricular repolarization without rate dependence.     

Evolution of the Organization of Epicardial Activation Patterns During Ventricular Fibrillation

Activation During Ventricular Fibrillation. Introduction : This study quantified how the organization of epicardial activation changes during the first 40 seconds of ventricular fibrillation (VF).
Activation During Ventricular Fibrillation. Introduction : This study quantified how the organization of epicardial activation changes during the first 40 seconds of ventricular fibrillation (VF).
Methods and Results : Unipolar potentials were mapped from a 504 (24 × 21) electrode array (2-mm interelectrode spacing) on the anterior right ventricle (RV) and left ventricle (LV) epicardium. The array covered approximately 20% of the epicardial surface. In each of seven pigs, six episodes of VF were induced by premature stimulation. One-half second epochs of VF were analyzed, starting 0, 10, 20, 30, and 40 seconds post induction and using novel pattern analysis algorithms. Eight parameters were quantified: (1) the number of wavefronts; (2) the epicardial area activated by wavefronts; (3) the fraction of wavefronts arising from epicardial breakthrough or from a focus; (4) the fraction of wavefronts terminated by conduction block; (5) the multiplicity index (number of distinct activation pathways in the rhythm); (6) the repeatability index (number of times activation pathways are traversed); (7) the activation rate; and (8) the wavefront propagation velocity. The results showed that VF patterns were less organized at 10 than at 0 seconds, with more, smaller wavefronts traversing a larger variety of pathways for fewer repetitions. VF activation patterns then gradually reorganized up to 40 seconds, but by a different mechanism: the spatial size of subpatterns grew, but the dynamics otherwise appeared unchanged. During both transitions, both activation rate and propagation velocity slowed monotonically.
Conclusion : Thus, changes in organization during VF can occur by multiple mechanisms.     

Excitable gap in canine fibrillating ventricular myocardium: effect of subacute and chronic myocardial infarction

INTRODUCTION: The existence of an excitable gap during ventricular fibrillation (VF) has been suggested in several prior studies. However, the effects of myocardial infarction on the presence and duration of an excitable gap during VF have not been evaluated. METHODS AND RESULTS: Electrophysiologic study was performed in normal dogs and in dogs with subacute and chronic infarction. Experimental infarction was produced by left anterior descending coronary ligation. The excitable gap was determined indirectly using either evaluation of intrinsic wavefronts during VF or from the shortest activation interval at individual sites using recordings from a 112-electrode plaque sutured to the epicardial surface of the left ventricle. The excitable gap also was correlated to local electrophysiologic and anatomic properties. The excitable gap using the wavefront propagation method and shortest activation method was significantly longer in subacute infarction dogs (48 +/- 17 msec and 37 +/- 18 msec, respectively) and chronic infarction dogs (41 +/- 14 msec and 35 +/- 14 msec, respectively) than normal dogs (32 +/- 13 msec and 30 +/- 11 msec, respectively; P < 0.05 normal vs subacute and chronic infarction dogs in both methods). The excitable gap occupied approximately 30% and 27% of the VF cycle length in all three groups using the wavefront propagation and shortest activation method, respectively. The excitable gap correlated better with local ventricular refractoriness determined using the wavefront propagation method than with the shortest activation method, but not at all with refractoriness determined using extrastimulus testing. Tissue necrosis was noted in subacute infarction dogs and fibrosis in chronic infarction dogs, but the gap was not highly correlated with anatomic changes. CONCLUSION: During VF, an excitable gap exists in both normal and infarcted canine ventricular myocardium. It is significantly longer in the presence of infarction. These finding have implications for understanding the pathophysiology of VF and targeting antiarrhythmic therapies.     

Clinical predictors of defibrillation threshold in patients with implantable cardioverter-defibrillators

BACKGROUND: Safety of patients with malignant ventricular arrhythmias, treated with implantable cardioverter defibrillators (ICD), depends on the possibility of immediate and effective intracardiac defibrillation. It is especially important in those patients in whom there is a risk of increased defibrillation threshold (DFT) of ventricular fibrillation (VF). Thus, it is important to know whether some clinical parameters may predict a high DFT. AIM: To assess the relationship between DFT and clinical, demographic and anthropometric parameters, type and progression of underlying disease as well as antiarrhythmic therapy used in ICD recipients. METHODS: The study group consisted of 168 patients (47 females, 121 males, mean age 55+/-15 years, range 15-82 years) who were selected to receive an ICD. DFT was systematically tested during ICD implantation in all patients. Various clinical, demographic, anthropometric and echocardiographic parameters were analysed as the function of DFT value, examining their accuracy in predicting a high (> or =15 J) or a low (<15 J) DFT, using logistic regression model. RESULTS: Univariate analysis revealed that DFT value was significantly related to the following parameters: idiopathic VF, dilated cardiomyopathy, amiodarone therapy and the use of beta blockers. There was a significant correlation between DFT and LVEDD, height, LVEF and impedance of defibrillating system. Multivariate analysis showed that amiodarone therapy, height, impedance of defibrillating system and LVEDD were independently related to the DFT value. Parameters which predicted a high (> or =15 J) DFT, consisted of amiodarone therapy (p=0.005), height (p=0.01), LVEDD (p=0.01), LVEF (p=0.03), dilated cardiomyopathy (p=0.01) and body surface area (p=0.049). Amiodarone therapy occurred to be the only parameter which independently predicted a high DFT (odds ratio 2.78; 95% confidence interval 1.19-6.5). CONCLUSIONS: Tall stature, enhanced LVEDD, decreased LVEF and amiodarone therapy increase the risk of a high DFT in ICD recipients. Chronic amiodarone therapy increases three times the risk of elevated DFT. In patients with already implanted ICD in whom amiodarone is started, reassessment of DFT following administration of a loading dose of the drug is required.     

The effect of induction method on defibrillation threshold and ventricular fibrillation cycle length

INTRODUCTION: Since no clinical data are available on the comparison of the "shock on T-wave" and "high frequency burst" ventricular fibrillation (VF) induction modes during defibrillation threshold (DFT) testing, we aimed to compare these two methods during implantable cardioverter defibrillator implantation. METHODS: The DFT was determined with a step-down protocol using biphasic, anodal polarity (100%, 40%, 20% voltage control) shocks. Patients were randomized: VF was induced by 50 Hz burst in group B (n = 45) and T-wave shock in group T (n = 41). The DFT was defined as the lowest energy level that terminated VF; confirmed DFT (DFTc) was defined as the minimal energy level that consecutively terminated VF twice. Success rate of DFTc was calculated during an intraindividual test for the alternate induction method. RESULTS: A total of 546 episodes of VF were induced: n = 278 (B) vs n = 268 (T). Incidence of VT during inductions was 9.9% (B) vs 2.7% (T), P < 0.05. Neither the DFT, 8.8 +/- 4.0 J (B) vs 9.7 +/- 4.2 J (T), nor the DFTc, 10.6 +/- 5.1 J (B) vs 10.8 +/- 4.2 J (T), proved to be significantly different. A significant correlation was found between VF cycle length (CL) and the concomitant DFT (r = 0.298, P < 0.05) in group T only. Subgroup analysis of patients under chronic class III antiarrhythmic treatment showed no increase of the DFT in either group and significantly lower incidence of VT induction in group T regardless of antiarrhythmic treatment. CONCLUSION: The DFT and the VFCL proved to be independent of the VF induction method. The T-wave shock was more unlikely to induce VT during DFT testing. These results suggest that both methods are reliable in DFT determination, though T-wave shock application is a more reliable method for DFT testing.     

Acute amiodarone promotes drift and early termination of spiral wave re-entry

Intravenous application of amiodarone is commonly used in the treatment of life-threatening arrhythmias, but the underlying mechanism is not fully understood. The purpose of the present study is to investigate the acute effects of amiodarone on spiral wave (SW) re-entry, the primary organization machinery of ventricular tachycardia/fibrillation (VT/VF), in comparison with lidocaine. A two-dimensional ventricular myocardial layer was obtained from 24 Langendorff-perfused rabbit hearts, and epicardial excitations were analyzed by high-resolution optical mapping. During basic stimulation, amiodarone (5 μM) caused prolongation of action potential duration (APD) by 5.6%–9.1%, whereas lidocaine (15 μM) caused APD shortening by 5.0%–6.4%. Amiodarone and lidocaine reduced conduction velocity similarly. Ventricular tachycardias induced by DC stimulation in the presence of amiodarone were of shorter duration (sustained-VTs >30 s/total VTs: 2/58, amiodarone vs 13/52, control), whereas those with lidocaine were of longer duration (22/73, lidocaine vs 14/58, control). Amiodarone caused prolongation of VT cycle length and destabilization of SW re-entry, which is characterized by marked prolongation of functional block lines, frequent wavefront-tail interactions near the rotation center, and considerable drift, leading to its early annihilation via collision with anatomical boundaries. Spiral wave re-entry in the presence of lidocaine was more stabilized than in control. In the anisotropic ventricular myocardium, amiodarone destabilizes SW re-entry facilitating its early termination. Lidocaine, in contrast, stabilizes SW re-entry resulting in its persistence.     

心肌梗死后心率变异性,压力反射敏感性与心肌电生理特性？…

目的 探讨心率变异性（ＨＲＶ）、压力反射敏感性（ＢＲＳ）预测心肌梗死（心梗）后心脏性猝死的电生理基础。方法 ４８只心梗兔分别测量ＨＲＶ时域与频域指标,ＢＲＳ、以有效不应期离散性（ＶＥＲＰ＿Ｄ）、室颤阈值（ＶＦＴ）,各指标进行相关性分析。结果根据电刺激能否诱发心室颤动（室颤）分为室颤组（ｎ＝２５）和无室颤组（ｎ＝２３）,室颤组的心率变异系数、极低频、低频、高频、ＲＢＳ和ＶＦＴ明显降低,ＶＥＲＰ－Ｄ     

Is all Ventricular Fibrillation the Same?

INTRODUCTION: Little information is available on the relationship between the mode of induction of ventricular fibrillation (VF) to VF characteristics. METHODS AND RESULTS: VF was induced from the anterior left ventricle by programmed electrical stimulation, burst pacing, alternating current (AC), high current S2 at a site remote from S1, T wave shock, and intersecting wavefronts in seven normal dogs and seven dogs with chronic myocardial infarction. Using two electrode arrays, 112 electrograms were recorded from the anterior and lateral wall. Cycle lengths were analyzed and activation vectors were created by summing orthogonally recorded bipolar electrograms. The magnitude of the vector loops was integrated over time to produce an "ensemble vector" index (EVI) whose magnitude is high when beat-to-beat activation direction is consistent and low when activation direction is variable. T wave shock-induced VF had a significantly longer cycle length 1 to 5 seconds after VF onset than other modes of induction (P < 0.05). The frequency-corrected EVI was significantly larger for AC current and T wave shock-induced VF as opposed to all other modes of VF induction in early VF (P < 0.0001). After 10 seconds of VF, these differences persisted only on the anterior wall. CONCLUSION: VF induced in animals by T wave shock and AC current had different characteristics than VF induced by other methods. These findings may have implications for our understanding of VF pathophysiology.     

Epicardial organization of human ventricular fibrillation.

OBJECTIVE: The objective of this study was to test the hypothesis that on the epicardium of the in vivo human heart, ventricular fibrillation (VF) consists of chaotic small wavefronts that constantly change paths. BACKGROUND: Despite the significance of VF to cardiovascular mortality, little is known about the wavefronts that constitute VF in humans. METHODS: In 9 patients undergoing cardiac surgery, a single VF episode was induced by rapid pacing immediately after institution of cardiopulmonary bypass while recordings were made from 504 electrodes spaced 2 mm apart in a 20 cm(2) plaque held against the anterior left ventricle epicardium. A total of 26 segments of VF, each 2 s long, were analyzed. A computer algorithm identified individual wavefronts and classified them into groups that followed similar activation sequences. RESULTS: The mean activation rate was 5.8 +/- 1.8 (mean +/- SD) cycles/s. The wavefronts during each epoch were grouped into 9.4 +/- 7.1 different activation pathways, and 8.3 +/- 2.3 wavefronts followed each pathway. Individual wavefronts spread to activate an area of 5.1 +/- 3.0 cm(2) in the mapped region. The majority of the wavefronts propagated into the mapped region and/or propagated out of the mapped region into adjacent tissue, suggesting that the wavefronts were larger than 5.1 cm(2). Reentry was identified in only 16 of the 26 (62%) 2-s segments, always completed <2 cycles, and lasted for 9.5 +/- 6.6% of these 16 epochs, which is 5.8% of the total duration of all the segments analyzed. CONCLUSION: VF wavefronts on the human epicardium are usually large, repeatedly follow distinct pathways, and only occasionally reenter. If these results for the left ventricular epicardium are representative of those for the entire ventricular mass, they do not support the hypothesis that human VF consists of small, constantly changing wavefronts, but rather suggest that there is significant organization of human VF.     

Antiarrhythmic drugs preferentially produce conduction block at the area of slow conduction in the re-entrant circuit of canine atrial flutter: comparative study of disopyramide, flecainide, and E-4031

STUDY OBJECTIVE--The aim was to test whether antiarrhythmic drugs preferentially suppressed conduction in the area of slow conduction in the re-entrant circuit. DESIGN--Intravenous disopyramide [n = 8, plasma concentrations: 1.4 (SEM 0.2) micrograms.ml-1], flecainide [n = 8, 0.6(0.1) micrograms.ml-1], and E-4031, a new class III antiarrhythmic drug [n = 8, 5.6(1.0) ng.ml-1], were investigated for their effects on atrial flutter due to re-entry in dogs with intercaval crush. In three dogs, detailed atrial activation sequence during atrial flutter was determined with a hand held bipolar electrode and an epicardial isochronal map was drawn. EXPERIMENTAL MATERIAL--24 anaesthetised adult mongrel dogs were used. MEASUREMENTS AND MAIN RESULTS--There was an area of slow conduction during atrial flutter in the low right atrium. Atrial flutter was terminated in all dogs except for one treated with flecainide. In 92% of the dogs, conduction block occurred in the low right atrium in which the area of slow conduction was located. Increase in local conduction time was greater in the area of slow conduction than other parts of the atria (percent ratio to the increase in cycle length of atrial flutter: 63% with disopyramide, 52% with flecainide, and 99% with E-4031). CONCLUSION--These data suggested antiarrhythmic drugs preferentially suppressed conduction at the area of slow conduction in the re-entrant circuit leading to termination of atrial flutter in this canine model, irrespective of electrophysiological effects of antiarrhythmic drugs.     

Electrophysiologic study-guided amiodarone for sustained ventricular tachyarrhythmias associated with structural heart diseases.

BACKGROUND: Although an electrophysiologic study (EPS) and Holter-monitoring are often helpful in evaluating the efficacy of antiarrhythmic drugs in patients with ventricular tachyarrhythmias (ventricular tachycardia/fibrillation (VT/VF)), the efficacy of EPS- or Holter-guided oral amiodarone therapy in Japanese patients is still unclear. METHODS AND RESULTS: EPS was performed 1 month after starting amiodarone, and Holter-monitoring was recorded before and 1 month after amiodarone in 188 patients with sustained VT/VF because of structural heart diseases. In spite of the judgment of EPS (n=89) or Holter (n=75), all patients continued amiodarone. Patients were followed up to 3 years and the primary endpoint was VT/VF recurrence and secondary endpoint was death by all cause. Kaplan-Meier estimated the risk of VT/VF recurrence was significantly smaller with EPS-guided amiodarone (p<0.01) but not with Holter-guided amiodarone. Multivariate Cox hazard analysis revealed that EPS-guided amiodarone was an independent factor suppressing the recurrence of VT/VF (p<0.05, 95% confidence interval =0.15 to 0.96). In the subgroup analysis, EPS-guided amiodarone was effective in patients with relatively well-preserved left ventricular ejection fraction (LVEF > or =0.30) but not in patients with lower LVEF (LVEF <0.30). CONCLUSION: EPS-guided amiodarone was useful for preventing recurrence of VT/VF in patients with a relatively well-preserved LVEF, but not always beneficial in patients with a lower LVEF.     

Rapid and stable re-entry within the pulmonary vein as a mechanism initiating paroxysmal atrial fibrillation

OBJECTIVES: We investigated the hypothesis that re-entrant pulmonary vein (PV) tachycardias may serve as a mechanism for initiating and sustaining paroxysmal atrial fibrillation (PAF). BACKGROUND: The mechanisms of rapid repetitive discharges from the PV initiating PAF remain incompletely understood. Pulmonary vein myocardial sleeves appear to provide a favorable substrate for re-entry formation. METHODS: The electrophysiologic properties of canine PV sleeves were investigated using a combination of high-resolution optical mapping (n = 5) and extracellular bipolar and intracellular microelectrode recordings (n = 56) in a superfused PV preparation. RESULTS: From the left atrium to distal PV, there was progressive shortening of the action potential (AP) duration, reduction in AP and bipolar electrogram amplitude, and depolarization of resting membrane potentials. Sustained PV tachycardias were induced exclusively in the presence of acetylcholine (10(-7) to 10(-6) mol/l, n = 12). Sustained PV tachycardias were rapid (mean cycle length = 93 +/- 15 ms), regular, and capable of induction, termination, and resetting by single extrastimuli. Re-entry as the mechanism underlying PV tachycardias was confirmed by optical mapping (n = 5). Acetylcholine also reduced the slope of the AP restitution curve and suppressed AP alternans (n = 6). Importantly, PV tachycardias exhibited 1:1 conduction into the atrium at short cycle lengths (<100 ms), emphasizing the potential role of re-entrant PV tachycardia in atrial fibrillation. CONCLUSIONS: Pulmonary veins provide a favorable substrate for re-entry formation. Heterogeneity of the electrophysiologic properties and marked abbreviation of action potential duration and refractoriness by acetylcholine combine to produce rapid and stable re-entrant PV tachycardias. Elevated parasympathetic tone and re-entrant PV tachycardia may serve as a mechanism underlying the perpetuation of PAF.     

Long-term efficacy and toxicity of high-dose amiodarone therapy for ventricular tachycardia or ventricular fibrillation

Amiodarone was administered to 154 patients who had sustained, symptomatic ventricular tachycardia (VT) (n = 118) or a cardiac arrest (n = 36) and who were refractory to conventional antiarrhythmic drugs. The loading dose was 800 mg/day for 6 weeks and the maintenance dose was 600 mg/day. Sixty-nine percent of patients continued treatment with amiodarone and had no recurrence of symptomatic VT or ventricular fibrillation (VF) over a follow-up of 6 to 52 months (mean ± standard deviation 14.2 ± 8.2). Six percent of the patients had a nonfatal recurrence of VT and were successfully managed by continuing amiodarone at a higher dose or by the addition of a conventional antiarrhythmic drug. One or more adverse drug reactions occurred in 51% of patients. Adverse effects forced a reduction in the dose of amiodarone in 41 % and discontinuation of amiodarone in 10% of patients. The most common symptomatic adverse reactions were tremor or ataxia (35 %), nausea and anorexia (8%), visual halos or blurring (6%), thyroid function abnormalities (6%) and pulmonary interstitial infiltrates (5%).Although large-dose amiodarone is highly effective in the long-term treatment of VT or VF refractory to conventional antiarrhythmic drugs, it causes significant toxicity in approximately 50% of patients. However, when the dose is adjusted based on clinical response or the development of adverse effects, 75 % of patients with VT or VF can be successfully managed with amiodarone.     

Potent Antiarrhythmic Effects of Chronic Amiodarone in Canine Pulmonary Vein Sleeve Preparations

Objectives: To examine the effects of chronic amiodarone on the electrophysiology of canine pulmonary vein (PV) sleeve preparations and left ventricular wedge preparation.
Background: Amiodarone is commonly used for the treatment of ventricular and supraventricular arrhythmias. Ectopic activity arising from the PV plays a prominent role in the development of atrial fibrillation (AF).
Methods: Standard microelectrode techniques were used to evaluate the electrophysiological characteristics of superfused PV sleeve (left superior or inferior) and arterially perfused left ventricular (LV) wedge preparations isolated from untreated and chronic amiodarone-treated dogs (amiodarone, 40 mg/kg daily for 6 weeks).
Results: In PV sleeves, chronic amiodarone (n = 6) induced a significant increase in action potential duration at 90% repolarization (APD₉₀) and a significant use-dependent reduction in V_max leading to 1:1 activation failure at long cycle lengths (basic cycle length of 124 ± 15 ms in control vs 420 ± 320 ms after chronic amiodarone [P < 0.01]). Diastolic threshold of excitation increased from 0.3 ± 0.2 to 1.8 ± 0.7 mA (P < 0.01). Delayed and late phase 3 early afterdepolarizations and triggered activity could be induced in PV sleeve preparations using acetylcholine (ACh, 1 μM), high calcium ([Ca²⁺]_o= 5.4 mM), isoproterenol (Iso, 1 μM), or their combination in 6 of 6 untreated PV sleeves, but in only 1 of 5 chronic amiodarone-treated PV sleeve preparations. V_max, conduction velocity, and 1:1 activation failure were much more affected in PV sleeves versus LV wedge preparations isolated from amiodarone-treated animals.
Conclusions: The results point to potent effects of chronic amiodarone to preferentially suppress arrhythmogenic substrates and triggers arising from the PV sleeves of the dog.     

Role of structural complexities of septal tissue in maintaining ventricular fibrillation in isolated, perfused canine ventricle

INTRODUCTION: It is unclear how the patterns of wavelet propagation during ventricular fibrillation (VF) vary between structurally different tissues. We hypothesized that the structural complexities of septal tissue influence the maintenance of reentrant wavelets in the ventricle. METHODS AND RESULTS: Endocardial activation patterns during VF were analyzed in the isolated, perfused canine right ventricular (RV) free wall (n = 9), interventricular septum (n = 5), and left ventricular (LV) free wall (n = 6) using a computerized mapping system (2-mm resolution) with 120-msec consecutive windows. Each tissue sample was cut progressively to reduce the tissue mass until the VF was terminated. More wavelets were seen in the septa than in the RV and LV free walls at baseline (P = 0.004), and VF in the septa displayed a shorter cycle length than in the RV and LV free walls (P = 0.017). As the tissue mass decreased, VF became successively more organized in all regions: the number of wavelets decreased and the cycle length of VF lengthened. Single and "figure-of-eight" stationary, reentrant wavelets often were mapped after tissue mass reduction in the RV free walls and rarely in the LV free walls, but they were not observed in the septa. Less critical mass was required to maintain VF in the septa than in the RV and LV free walls (P = 0.0006). Gross anatomic and histologic examinations indicated that the tissue structure of the septa is more complex than that of the RV and LV free walls. CONCLUSION: VF activation patterns with progressive reduction of tissue mass differ for the septum and the ventricular free walls. The structural complexities of the septal tissue influence the maintenance of fibrillation in the ventricle.     

Electrophysiological effects of neferine against ischemic ventricular tachyarrhythmias]

The electrophysiological effects of neferine (Nef, 8mg/kg,i.v.) on ischemic ventricular tachyarrhythmias in both normal and ischemic myocardium were studied in open-chest dogs by programmed electrical stimulation (PES) with intimal surface anodal direct current at the circumflex coronary artery during 5-8 days after acute myocardial infarction. Its effects were compared with procainamide (PA). Both drugs lengthened the QTc interval and the effective refractory period (ERP) of normal and infarcted myocardium in both ventricles and decreased the dispersion of ERP in infarcted myocardium (IDR) as well as in left ventricle (VDR), increased the diastolic excitability threshold (DET) of normal and infarcted myocardium in both ventricles remarkably. The PES-induced VT or VF was prevented in all of Nef treated dogs and in 5 out of 6 PA treated dogs, Nef prevented spontaneous VF in 5 dogs (n = 6), PA prevented spontaneous VF in 4 dogs (n = 6). The results indicated that Nef may be effective in preventing the onset of reentrant ventricular tachycardias and sudden cardiac death after myocardial ischemic damage.     

Noninvasive Mapping of Human Atrial Fibrillation

Introduction: Invasive high-density mapping of atrial fibrillation (AF) has revealed different patterns of atrial activation ranging from single wavefronts to disorganized activation with multiple simultaneous wavefronts. Whether or not similar activation patterns can also be observed using body surface recordings is currently unknown, and was consequently evaluated in this study.
Methods and Results: Surface electrocardiographic mapping was performed in 14 patients (age 68 ± 14 years) with persistent AF (AF duration 12 ± 18 months). A total of 56 electrocardiographic leads were placed on the chest over the atria on the front (n = 40) and on the back (n = 16). Using 240-second recordings, wavefront propagation maps were automatically computed and visually classified as either type I (single wavefront), II (single wavefront with wave breakages and splitting), or III (multiple simultaneous wavefronts). Almost half of the patients (n = 6) presented most predominantly type III atrial activation, while six patients mostly presented type I activation. The rest of the patients (n = 2) presented mixed type I and type III activations. This classification showed to be highly reproducible over 4 minutes.
Conclusions: Using electrocardiographic body surface mapping during AF, interindividual differences of atrial fibrillatory activation can be observed. The surface activation pattern during AF shows an excellent short-term reproducibility.     

Pacing following shocks stronger than the defibrillation threshold: impact on defibrillation outcome

INTRODUCTION: A recent study of shocks near defibrillation threshold (DFT) strength demonstrated that at least three rapid cycles always occur after failed shocks but not after successful shocks, suggesting that the number and rapidity of postshock cycles are important in determining defibrillation success. To test this hypothesis, rapid pacing was performed following a shock stronger than the DFT that by itself did not induce rapid cycles and ventricular fibrillation (VF). METHODS AND RESULTS: Epicardial activation was mapped in six pigs using a 504-electrode sock. The DFT was determined by an up/down protocol with S1 shocks (right ventricle-superior vena cava, biphasic). Ten shocks that were 100 to 200 V above the DFT (aDFT) were delivered after 10 seconds of VF to confirm they always defibrillated. Then, S2, S3, etc., pacing at 5 to 10 times diastolic threshold was performed from the left ventricular apex after aDFT shocks during VF. First, the postshock interval after aDFT shocks was scanned with an S2 stimulus to find the shortest S1-S2 coupling interval (CI) that captured. This was repeated for S3, S4, etc., until VF was induced. To induce VF after aDFT shocks, three pacing stimuli (S2, S3, S4) with progressively shorter CIs were always required; S2 or S2,S3 never induced VF. For the S2-S4 cycles, the intercycle interval was shorter (P < 0.01), and the wavefront conduction time was longer (P < 0.01) for episodes in which VF was induced (n = 57) than for episodes in which it was not (n = 60). Following the S4 cycle that induced VF, two types of spontaneous activation patterns appeared: focal (88%) and reentrant (12%). CONCLUSION: VF induction after aDFT shocks always required at least three rapid successive paced-induced cycles. Thus, the number and rapidity of the first several postshock cycles rather than just the first postshock cycle may be determining factors for defibrillation outcome.