Recombinant Lactococcus lactis Expressing Ling Zhi 8 Protein Ameliorates Nonalcoholic Fatty Liver and Early Atherogenesis in Cholesterol-Fed Rabbits.

Atherosclerosis is an inflammatory disease characterized by lipid deposits in the subendothelial space leading to severe inflammation. Nonalcoholic fatty liver disease (NAFLD) shares several risk factors with atherosclerosis, including dyslipidemia, type 2 diabetes mellitus, and metabolic syndrome, all of which lead to lipid deposition in the liver causing inflammation and fibrosis. Several clinical trials have shown that certain Chinese herbal medicines with anti-inflammatory effects can be used as adjuvant therapy to prevent the development of cardiovascular events and liver disease. Ling Zhi 8 (LZ8) is an immunomodulatory protein isolated from a medicinal mushroom and has been well documented to possess a broad range of pharmacological properties. This study aimed to evaluate the protective effects of recombinant Lactococcus lactis expressing LZ8 protein on NAFLD and atherogenesis in a cholesterol-fed rabbit model. Twelve rabbits were divided into three groups and fed with syrup only, L. lactis vehicle, or recombinant L. lactis-LZ8 once a day on weekdays for five weeks, respectively. The gene expression of IL-1ß in the aorta was significantly suppressed after oral administration of L. lactis-LZ8. Moreover, in hematoxylin and eosin staining of the aorta, the intima-medial thickness was decreased, and foam cells were significantly reduced in the subendothelial space. LZ8 also inhibited the expression of IL-1ß in the liver, decreased fat droplet deposits and infiltration of inflammatory cells, and improved liver function by decreasing liver enzymes in an animal model. Our results suggest that the Lactococcus-expressing LZ8 appears to be a promising medicine for improving both NAFLD and early atherogenesis owing to its anti-inflammatory effect. Furthermore, it is available as a low-cost food-grade product.

Heterogeneous distribution of substrates between the endocardium and epicardium promotes ventricular fibrillation in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Aims: Whether the distribution of scar in arrhythmogenic right ventricular cardiomyopathy (ARVC) plays a role in predicting different types of ventricular arrhythmias is unknown. This study aimed to investigate the prognostic value of scar distribution in patients with ARVC. Methods and results: We studied 80 consecutive ARVC patients (46 men, mean age 47 ± 15 years) who underwent an electrophysiological study with ablation. Thirty-four patients receive both endocardial and epicardial mapping. Abnormal endocardial substrates and epicardial substrates were characterized. Three groups were defined according to the epicardial and endocardial scar gradient (<10%: transmural, 10-20%: intermediate, >20%: horizontal, as groups 1, 2, and 3, respectively). Sinus rhythm electrograms underwent a Hilbert-Huang spectral analysis and were displayed as 3D Simultaneous Amplitude Frequency Electrogram Transformation (SAFE-T) maps, which represented the arrhythmogenic potentials. The baseline characteristics were similar between the three groups. Group 3 patients had a higher incidence of fatal ventricular arrhythmias requiring defibrillation and cardiac arrest during the initial presentation despite having fewer premature ventricular complexes. A larger area of arrhythmogenic potentials in the epicardium was observed in patients with horizontal scar. The epicardial-endocardial scar gradient was independently associated with the occurrence of fatal ventricular arrhythmias after a multivariate adjustment. The total, ventricular tachycardia, and VF recurrent rates were higher in Group 3 during 38 ± 21 months of follow-up. Conclusion: For ARVC, the epicardial substrate that extended in the horizontal plane rather than transmurally provided the arrhythmogenic substrate for a fatal ventricular arrhythmia circuit.

Left Atrial Size and Left Ventricular End-Systolic Dimension Predict the Progression of Paroxysmal Atrial Fibrillation After Catheter Ablation.

INTRODUCTION: Although rare, some paroxysmal atrial fibrillations (AF) still progress despite radiofrequency (RF) ablation. In the study, we evaluated the long-term efficacy of RF ablation and the predictors of AF progression. METHODS: A total of 589 paroxysmal AF patients (404 men and 185 women; aged 54 ± 12 years) who received 3-dimensional mapping and ablation were enrolled. Their clinical parameters and electrophysiological characteristics were collected. They were divided into Group 1 (N = 13, with AF progression) and Group 2 (N = 576, no AF progression). AF progression was defined as recurrence of persistent AF. RESULTS: Group 1 patients had larger left atrial (LA) diameter, larger left ventricle (LV) end-systolic and end-diastolic diameters, poorer LV systolic function, and more amiodarone use at baseline. After 1.2 ± 0.5 procedures, 123 (21%) patients experienced recurrence during 56 ± 29 months' follow-up. In the multivariate analysis, LA diameter (P = 0.018, HR = 1.12, 95% CI = 1.02-1.24) and LV end-systolic diameter (P = 0.005, HR = 1.10, 95% CI = 1.03-1.17) independently predicted AF progression. LA diameter >43 mm and LV end-systolic diameter >31 mm were the best cut-off values for predicting AF progression by ROC analysis. AF progression rate achieved 19% if they had both larger LA diameter (>43 mm) and LV end-systolic diameter (>31 mm). CONCLUSION: RF ablation prevents the progression of paroxysmal AF effectively, except in patients with increased LA diameter and LV end-systolic diameter on echocardiogram, suggesting more aggressive rhythm control therapies should be considered in these patients.

Electrophysiological characteristics of complex fractionated electrograms and high frequency activity in atrial fibrillation.

BACKGROUND: It is unclear whether atrial substrate with complex fractionated electrograms (CFAEs) is related to arrhythmogenesis. This study aimed to investigate the electrophysiology in CFAE and high dominant frequency (DF) areas. METHODS AND RESULTS: Atrial fibrillation (AF) was induced by rapid atrial pacing in heart failure (HF) rabbits (4 weeks after coronary artery ligation). Real-time substrate mapping, multielectrode array, and monophasic action potential recordings were used to study areas of CFAE and DF. Conventional microelectrode and western blot were used to record the action potentials (APs) and protein expression in isolated tissue preparations. CFAE site with high DF had the most depolarized resting membrane potential, highest incidence of early and delayed afterdepolarizations, and steepest maxima slope of 90% of AP duration (APD90) restitution curve (RC) compared to CFAE site with low DF or non-CFAE sites. CFAE site with high DF exhibited the slowest conduction velocity and shortest wavelength than the other areas. Upregulation of the Na(+)-Ca(2+) exchanger (NCX), apamin-sensitive small-conductance Ca(2+)-activated K(+) channel type 2 (SK2) and sarcoplasmic reticulum Ca(2+)-ATPase, and downregulation of the Kir2.1 were found at CFAE site with high DF compared to that observed in the 3 other areas. Inhibition of the NCX and SK channels prolonged the APD90, flattened the maximum slope of RC, and suppressed AF. CONCLUSIONS: CFAE site with high DF had an arrhythmogenic property differing significantly from the other areas of LA in an HF rabbit model, which may contribute to the genesis of AF.

Novel assessment of temporal variation in fractionated electrograms using histogram analysis of local fractionation interval in patients with persistent atrial fibrillation.

BACKGROUND: The characteristics of atrial electrograms associated with atrial fibrillation (AF) termination are controversial. We investigated the electrogram characteristics that indicate procedural AF termination during continuous complex fractionated electrogram ablation. METHODS AND RESULTS: Fifty-two consecutive patients with persistent AF (47 men; aged 54 ± 9 years), who underwent electrogram-based catheter ablation in the left atrium and coronary sinus after pulmonary vein isolation, were enrolled. The intracardiac bipolar atrial electrogram recordings were characterized by (1) fractionation interval (FI) analysis (>6 seconds), (2) kurtosis (shape of the FI histogram), and (3) skewness (asymmetry of the FI histogram). Sites showing complex, fractionated electrograms (mean FI ≤ 60 ms) were targeted, and AF was terminated in 20 patients (38%) after the pulmonary vein isolation. The conventional complex fractionated electrogram sites (mean ≤ 120 ms) in patients with AF termination exhibited higher median kurtosis (2.69 [interquartile range, 2.03-3.46] versus 2.35 [interquartile range, 1.79-2.48]; P=0.024) and higher complex fractionated electrogram-mean interval (102.7 ± 19.8 versus 87.7 ± 15.0; P=0.008) than patients without AF termination. Furthermore, AF termination sites had higher median kurtosis than targeted sites without AF termination (5.13 [interquartile range, 3.51-6.47] versus 4.18 [interquartile range, 2.91-5.34]; P<0.01) in patients with procedural termination. In addition, patients with AF termination had a higher sinus rhythm maintenance rate after a single procedure than patients without AF termination (log-rank test, P=0.007). CONCLUSIONS: A kurtosis analysis using the FI histogram may be a useful tool in identifying the critical substrate for persistent AF and potential responders to catheter ablation.

Comparison of quick optimization of interventricular delay between simple methods: intracardiac electrogram and surface electrocardiogram after cardiac resynchronization therapy.

AIMS: It is time consuming to obtain optimal interventricular (VV) delay by conventional methods. This study is designed to compare quick optimization between intracardiac electrogram (IEGM) with surface electrocardiogram (ECG)-guided VV delay optimization for cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Fifty-one heart failure patients (M/F = 34/17, age = 71 ± 10-year-old) scheduled for CRT implantation were included. After atrioventricular optimization, VV delay optimization was performed by either the IEGM or surface ECG method. Aortic velocity time integral (AVTI) was used  as a reference in comparing these two methods. Real-time three-dimensional echocardiography was studied under three varying parameters-CRT switched off or CRT switched on, and VV delay optimized by IEGM guided or surface ECG. The AVTI could be improved equally by either IEGM-guided or surface ECG-guided VV optimization. All the other parameters [QRS width, systolic dyssynchrony index (SDI), left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV)] could be improved by either the IEGM or ECG method in these patients. In the multivariate logistic regression analysis, the immediate improvement of acute LVEF was independently related to favourable outcomes (odds ratio 1.23, 95% CI = 1.03-1.47, P = 0.02). CONCLUSIONS: The AVTI, QRS width, SDI, LVEF, LVEDV, and LVESV could be improved equally by either IEGM-guided or surface ECG-guided method after CRT.

Relationship between the CHADS(2) score and risk of very late recurrences after catheter ablation of paroxysmal atrial fibrillation.

BACKGROUND: Catheter ablation of paroxysmal atrial fibrillation has been performed for more than 10 years. However, data about the long-term results were limited. OBJECTIVES: To evaluate the long-tem efficacy following paroxysmal atrial fibrillation ablation and to investigate whether there were different patterns of recurrences in patients with different CHADS(2) scores. METHODS: A total of 238 patients with paroxysmal atrial fibrillation who received a catheter ablation from 2004 to 2007 were enrolled. Free of recurrence was defined as the absence of atrial arrhythmias without using any antiarrhythmic agents after ablation. RESULTS: There were 121 patients (50.8%) suffering from recurrences after the first ablation procedure during a median follow-up period of 5 years. The CHADS(2) score and left atrial diameter were significant predictors of recurrences in the multivariate analysis. Different patterns of recurrence were observed in different groups of patients categorized on the base of CHADS(2) score. Among patients with a CHADS(2) score of ≥3 without recurrences at 2 years postablation, 63.6% experienced episodes of arrhythmias during the subsequent follow-up period. In contrast, in patients with a CHADS(2) score of 0 without recurrences at 2 years postablation, the future recurrence rate was only 2.7%. CONCLUSIONS: After a successful ablation, recurrences may continue to occur without reaching a plateau during the long-term follow-up, especially in patients with a high CHADS(2) score. The optimal follow-up strategy may differ and should be individualized for patients with different scores.

Heart failure enhances arrhythmogenesis in pulmonary veins.

1. Heart failure (HF) predisposes to atrial fibrillation (AF) as a result of substrate remodelling. The present study aimed to investigate the impact of HF on the electrical remodelling of the pulmonary veins (PV) and left atrium (LA). 2. The electrical activity was recorded in LA and PV from control rabbits and rabbits with rapid ventricular pacing-induced HF, using a multi-electrode array system and conventional microelectrodes. 3. Compared with the control-PV (n = 21), the HF-PV (n = 13) had a higher incidence and frequency of rapid pacing-induced spontaneous activity (85 vs 29%, P = 0.005; 3.5 ± 0.2 vs 1.7 ± 0.1 Hz, P < 0.001) and high-frequency irregular electrical activity (92 vs 38%, P = 0.01; 23 ± 1 vs 19 ± 1 Hz, P = 0.003), greater depolarized resting membrane potential (-59 ± 1 vs -70 ± 2 mV, P < 0.001), higher incidence of early afterdepolarizations (EAD; 69 vs 6%, P = 0.001) and delayed afterdepolarizations (DAD; 92 vs 25%, P = 0.001), and slower conduction velocity (38 ± 2 vs 63 ± 2 cm/s, P < 0.05). In comparison to the HF-LA, the HF-PV had a higher incidence of spontaneous activity and high-frequency irregular electrical activity (85 vs 39%, P = 0.04; 92 vs 46%, P = 0.03), and higher incidence of EAD and DAD, and those differences were not found between the control-LA and control-PV. The control-PV with high-frequency irregular electrical activity had a higher incidence of DAD and spontaneous activity as compared with those without it. 4. HF contributed to an increased automaticity, triggered activity and conduction disturbance in the PV. The PV possessed more arrhythmogenic properties, which might play an important role in the genesis of AF in HF.

Characteristics and significance of very early recurrence of atrial fibrillation after catheter ablation.

INTRODUCTION: Early restoration of sinus rhythm following ablation of atrial fibrillation (AF) facilitates reverse atrial remodeling and improves the long-term outcome. The purpose of this study was to determine the predictors and outcome in patients with very early AF recurrences (< 2 days). METHODS AND RESULTS: Ablation was performed in 339 consecutive AF patients (paroxysmal AF = 262). Biatrial voltage was mapped during sinus rhythm. If recurrent AF occurred within 2 days following the ablation, electrical cardioversion was performed to restore sinus rhythm. Very early recurrences of AF occurred in 39 (15%) patients with paroxysmal AF and 26 (34%) with nonparoxysmal AF. Patients with very early recurrence had a higher incidence of nonparoxysmal AF (40% vs 18.6%, P< 0.001), requirement of electrical cardioversion during procedure, larger left atrial (LA) diameter (43 ± 7 vs 39 ± 6 mm, P< 0.001), lower left ventricular ejection fraction (54 ± 10% vs 59 ± 7, P< 0.001), longer procedural time, and lower LA voltage (1.5 ± 0.7 vs 1.9 ± 0.8 mV, P< 0.001). A multivariate analysis revealed that the independent predictors of a very early recurrence were a longer procedural time and lower LA voltage. During a follow-up of 13 ± 5 months, a very early recurrence did not predict the long-term outcome of a single procedure recurrence in the patients with paroxysmal AF, but was associated with a late recurrence in the nonparoxysmal AF patients. CONCLUSION: Very early recurrence occurred in patients with paroxysmal AF is not associated with long-term recurrence. Nonparoxysmal AF is an independent predictor of late recurrence of AF in patients with very early recurrence.

Associations among the CHADS(2) score, atrial substrate properties, and outcome of catheter ablation in patients with paroxysmal atrial fibrillation.

BACKGROUND: The CHADS2 score (congestive heart failure, hypertension, age >75 years, diabetes, and previous stroke/transient ischemic attack) is used for the risk stratification of strokes in patients with atrial fibrillation (AF). OBJECTIVE: This study aimed to investigate the associations between the CHADS2 score, atrial substrate, and outcome of catheter ablation in patients with paroxysmal AF. METHODS: A total of 247 paroxysmal AF patients who received catheter ablation were enrolled. The patients were divided into 3 groups according to their CHADS2 score (group 1: score 0, group 2: score 1 to 2, and group 3: score 3 to 6). The bi-atrial substrate properties and outcome of catheter ablation were analyzed. RESULTS: The CHADS2 scores in these 3 groups were 0 (group 1), 1.24 ± 0.48 (group 2), and 3.60 ± 0.83 (group 3), respectively. The left atrial voltage became lower (group 1 vs. 2 vs. 3 = 2.08 ± 0.73 mV vs. 1.80 ± 0.81 mV vs. 1.06 ± 0.69 mV) and the activation time longer (group 1 vs. 2 vs. 3 = 93.4 ± 17.7 ms vs. 101.9 ± 21.2 ms vs. 112.2 ± 21.7 ms), whereas the CHADS2 score increased. During a follow-up of 17.3 ± 7.0 months, 23.1% of the study population suffered from recurrences. The recurrence rates of these 3 groups were 13.0% (group 1), 27.6% (group 2), and 45.9% (group 3), respectively. The groups of different CHADS2 scores remained as the independent predictor of recurrence in the multivariate analysis. CONCLUSION: A high CHADS2 score was associated with different left atrial substrate properties and a poor outcome after catheter ablation of paroxysmal AF.

Characterization of the dynamic function of the pulmonary veins before and after atrial fibrillation ablation using multi-detector computed tomographic images.

Understanding pulmonary vein (PV) function before and after catheter ablation can validate the benefit of the treatment and provide mechanistic insight into atrial fibrillation (AF). This study was aimed to investigate the functional remodeling process of PVs by multi-detector computed tomography (MDCT). We assessed the dynamic function of four PVs by MDCT at systolic and diastolic phases. Twelve points around each PV ostium were used to assess the magnitude and abnormalities of the regional wall motion. The axis of PV shifting during cardiac cycle was also determined. Seventy-four paroxysmal AF patients and 29 controls were enrolled. In those of AF, the superior PVs had poorer contractile function (ejection fraction: P = 0.01 for left; P = 0.009 for right; magnitude of the motion: P = 0.01 for left; P = 0.02 for right) which mainly resulted from the decreased movement of the posterior wall. In contrast, the function of inferior PVs was similar between two groups. After a mean follow-up of 158 ± 95 days, the PV motion improved in the patients without any AF recurrence. In addition, analysis of the pre-ablation PV function showed that the angles, which shifted during cardiac cycle of left (P = 0.035) and right (P = 0.014) inferior PV, were significantly decreased in recurrent patients. The contractile function of the superior PVs was impaired in paroxysmal AF patients. This was attributed to the hypokinesia of the posterior wall of PVs and improved after circumferential ablation in the patients without recurrence. MDCT images can effectively delineate the functional characteristics of PVs.

Green tea extract given before regional myocardial ischemia-reperfusion in rats improves myocardial contractility by attenuating calcium overload.

There is evidence for a negative correlation between green tea consumption and cardiovascular diseases. The aim of the present study was to examine whether green tea extract (GTE) given before regional myocardial ischemia could improve depression of myocardial contractility by preventing cytosolic Ca(2+) overload. Regional ischemia-reperfusion (IR) was induced in rats by ligating the left anterior descending branch for 20 min, then releasing the ligature. Ligation induced ventricular arrhythmias in rats without GTE pretreatment, but decreased arrhythmogenesis was seen in rats pretreated 30 min earlier with GTE (400 mg/kg). During reperfusion, arrhythmias only occurred during the initial 5 min, and GTE pretreatment had no effect. After overnight recovery, serum cTnI levels were greatly increased in control post-IR rats but only slightly elevated in GTE-pretreated post-IR rats. Myocardial contractility measured by echocardiography was still depressed after 3 days in control post-IR rats, but not in GTE-pretreated post-IR rats. No myocardial ischemic injury was seen in post-IR rats with or without GTE pretreatment. Using freshly isolated single heart myocytes, GTE was found to attenuate the post-IR injury-associated cytosolic Ca(2+) overload and modulate changes in the levels and distribution of myofibril, adherens junction, and gap junction proteins. In summary, GTE pretreatment protects cardiomyocytes from IR injury by preventing cytosolic Ca(2+) overload, myofibril disruption, and alterations in adherens and gap junction protein expression and distribution.

Repetitive endocardial focal discharges during ventricular fibrillation with prolonged global ischemia in isolated rabbit hearts.

BACKGROUND: Ventricular fibrillation (VF) during prolonged (>5 min) global ischemia (GI) could be due to repetitive endocardial focal discharges (REFDs). This hypothesis was tested in isolated rabbit hearts. METHODS AND RESULTS: With optical mapping, simultaneous endocardial (left ventricle, LV) and epicardial (both ventricles) activations during VF with prolonged GI were studied (protocol I, 8 hearts). Lugol solution was applied to the LV endocardium in additional 5 hearts after 5-min GI (protocol II). During prolonged GI, sustained VF (>30 s) was successfully induced in 7 protocol I hearts. The dominant frequency of summed optical signals at the LV endocardium was higher than at the epicardium (P<0.05). Mapping data showed that after 5-min GI, REFDs were present in >90% for recording time. There were 18 windows of optical recording showing spontaneous VF termination. In 10, once REFDs ceased, the VF episode terminated immediately. Electrical defibrillation was also performed on 3 hearts. Eight shocks showed early VF recurrence after successful defibrillation. REFDs were consistently involved in the initiation period of recurrence. In protocol II, Lugol subendocardial ablation diminished REFD genesis during re-induced VF. These VF episodes were all non-sustained. CONCLUSIONS: REFDs at the LV endocardium were important for both VF maintenance and post-shock recurrence during prolonged GI in this model.

Gender differences of electrophysiological characteristics in focal atrial tachycardia.

Gender differences of supraventricular tachycardias such as atrioventricular nodal re-entry, atrioventricular re-entry, and atrial fibrillation have been reported. There is little evidence of the effect of gender on focal atrial tachycardia (FAT). The study consisted of 298 patients who were referred to this institution for radiofrequency catheter ablation of FAT from October 1992 to April 2008 and included 156 men (52%) and 142 women (48%). Men were significantly older than women (57.9 +/- 18.2 vs 47.2 +/- 19.0 years old, p <0.001). Women had more associated arrhythmias (17.0% vs 28.9%, p = 0.01), mostly due to an increased incidence of atrioventricular nodal re-entrant tachycardia. Men had more cardiovascular co-morbidities (19.9% vs 9.9%, p = 0.02), a mechanism of increased automaticity (19.1% vs 8.1%, p = 0.01), and nonparoxysmal tachycardia (14.7% vs 4.4%, p = 0.01). No gender differences were noted among FAT number, left atrial involvement, shortest tachycardia cycle, success rate of catheter ablation, or recurrence rate of FAT. Mean duration of follow-up was 63.2 +/- 47.5 months. Premenopausal women had a lesser cardiovascular co-morbidity (15.3% vs 4.3%, p = 0.04) and a greater incidence of a mechanism of increased automaticity (13.4% vs 2.9%, p = 0.03). In conclusion, gender differences in electrophysiologic characteristics were noted in FAT.

d,l-Sotalol at therapeutic concentrations facilitates the occurrence of long-lasting non-stationary reentry during ventricular fibrillation in isolated rabbit hearts.

BACKGROUND: The effects of d,l-sotalol at therapeutic concentrations (

Coexistence of two types of ventricular fibrillation during acute regional ischemia in rabbit ventricle.

INTRODUCTION: We previously reported that a normal ventricle can demonstrate two types of ventricular fibrillation (VF), depending on the underlying electrophysiologic characteristics at the time of VF induction. We hypothesize that the two types of VF can coexist in acutely ischemic ventricles. METHODS AND RESULTS: Optical mapping studies were performed with di-4ANEPPS in 15 Langendorff-perfused rabbit hearts. Coronary artery branches were ligated to create regional ischemia in 10 hearts. Action potential duration measured to 50% repolarization (APD50) during ischemia showed an area with uniformly shortened APD50 (zone 1), an area with normal or lengthened APD50 (zone 3), and an area in between with an APD50 gradient (zone 2). Ischemia flattened APD restitution (APDR) slope and reduced conduction velocity in zone 1, creating a condition for type II VF. APDR steepened and the conduction velocity changed little in the nonischemic zone (zone 3), creating a condition for type I VF. During induced VF, the dominant frequency in zones 2 and 3 progressively increased after ischemia onset. The dominant frequency in zone 1 (ischemic zone) first decreased and then slightly increased but typically remained less than the dominant frequency in zone 3. The number of wavebreaks increased with time in all three zones (baseline: 4.3 +/- 1.5; 30 min: 11.7 +/- 5.6; 60 min: 15.6 +/- 11 per frame; P < 0.01). CONCLUSION: Two types of VF can coexist during acute regional ischemia. Both ischemic and nonischemic regions develop proarrhythmic changes during regional ischemia, thus contributing to increased ventricular vulnerability to VF and sudden death during acute coronary occlusion.

Electrophysiological mapping and histological examinations of the swine atrium with sustained (> or =24 h) atrial fibrillation: a suitable animal model for studying human atrial fibrillation.

OBJECTIVES: Interventional elimination of chronic persistent atrial fibrillation (AFib) remains difficult. An animal model mimicking the clinical situation is important. METHODS AND RESULTS: Twenty-five adult pigs were implanted with a high-speed atrial pacemaker. After continuous pacing at 600 bpm for 6 weeks, 20 (91%) of the 22 survivals developed sustained AFib lasting for at least 24 h. Epicardial dense mapping revealed multiple coexisting reentrant wavelets in the left and the right atrium (LA and RA, respectively; 10.6 +/- 2.9 vs. 7.6 +/- 2.4 wavelets/cm(2)/s; p < 0.002). The mean local A-A intervals were 87.2 +/- 14.6 ms in the LA and 103.3 +/- 19.0 ms in the RA (p < 0.0002). Acute termination of sustained AFib was successful in 3 of the 5 pigs by propafenone, but in none of the 6 by dl-sotalol. Epicardial cryothermal ablation failed to terminate any AFib by compartmentalization of the RA free wall alone (4 pigs) or together with the LA appendage (4 pigs). Electron microscopic examination demonstrated diffuse perinuclear myolysis, myofibrillar fragmentation and mitochondrial crystal disruption in the atrium. CONCLUSIONS: Pacing-induced sustained AFib (> or =24 h) in adult pigs is a feasible and efficient animal model with electrophysiological and histological characteristics closely similar to those seen in humans.

Two types of ventricular fibrillation in isolated rabbit hearts: importance of excitability and action potential duration restitution.

BACKGROUND: The combined effects of excitability and action potential duration (APD) restitution on wavefront dynamics remain unclear. METHODS AND RESULTS: We used optical mapping techniques to study Langendorff-perfused rabbit hearts. In protocol IA (n=10), D600 at increasing concentrations was infused during ventricular fibrillation (VF). With concentration increased to 0.5 mg/L, fast VF (dominant frequency, 19.1+/-1.8 Hz) was consistently converted to ventricular tachycardia (VT). However, increasing D600 further to 2.5 or 5.0 mg/L converted VT to slow VF (11.9+/-2.3 Hz, P=0.0011). In an additional 4 hearts (protocol IB), tetrodotoxin converted a preexisting VT to slow VF (11.0+/-1.4 Hz). Optical maps show wandering wavelets in fast VF, organized reentry in VT, and spatiotemporal periodicity in slow VF. In protocol II, we determined APD and conduction time(-1) (CT(-1)) restitutions during D600 infusion. CT(-1) was used as an estimate of excitability. At 0.1 mg/L, APD and CT(-1) restitutions were steep and flat, respectively. APD restitution became flattened when D600 increased to 0.5 mg/L, converting fast VF to VT. Further increasing D600 to 2.5 or 5.0 mg/L steepened CT(-1) restitution and widened the range of S(1) pacing cycle lengths over which CT(-1) decreased, converting VT to slow VF. CONCLUSIONS: Two types of VF exist in isolated rabbit hearts. Fast (type I) VF is associated with a steep APD restitution, a flat CT(-1) restitution, and wandering wavelets. Slow (type II) VF is associated with a flat APD restitution, a steep CT(-1) restitution, and spatiotemporal periodicity. Both excitability and APD restitution are important in VF maintenance.