RESUMEN
OBJECTIVES: To evaluate the preventive efficacy of multisite and septal atrial pacing in an experimental model. METHODS: Sterile right atrial pericarditis was induced in 12 foxhounds to provide an anatomical substrate for atrial fibrillation (AF). As a trigger mechanism, atrial extrasystoles were simulated by constant asynchronous pacing at a cycle length of 1000 ms from randomly selected right or left atrial electrodes, using a biatrial epicardial multielectrode with 128 bipoles. Additionally, a transvenous pacing lead was screwed into the interatrial septum. Four electrodes located in the high and low right (HRA/LRA) and left atrium (HLA/LLA) were selected for preventive multisite stimulation. Constant pacing at a cycle length 30 ms below sinus rate was applied from the following site(s): HRA, septal, HRA+LRA, HRA+LLA, HRA+LRA+LLA and HRA+LRA+HLA+LLA (order randomized). Number and duration of AF episodes were studied during 10 min intervals, separated by 5 min pauses, respectively. To validate the model, the protocol was repeated 10 min after i.v. bolus administration of D,L-sotalol (1 mg/kg body weight). RESULTS: The number of AF episodes decreased with increasing number of pacing sites, reaching statistical significance compared to HRA stimulation for quadruple-site and single-site septal pacing only (P<0.05). Single-site septal was as efficient as quadruple-site pacing in suppressing AF. The duration of AF episodes was not significantly affected by the pacing configuration. D,L-sotalol almost completely suppressed AF irrespective of the pacing configuration used. CONCLUSIONS: In this novel experimental model, quadruple-site and septal pacing effectively suppress paroxysmal AF.
Asunto(s)
Fibrilación Atrial/terapia , Estimulación Cardíaca Artificial/métodos , Antagonistas Adrenérgicos beta/farmacología , Análisis de Varianza , Animales , Perros , Atrios Cardíacos , Tabiques Cardíacos , Modelos Animales , Pericarditis , Sotalol/farmacologíaRESUMEN
Although, sodium channel blockers have the ability to suppress nonsustained ventricular arrhythmias, an excessive drug-associated arrhythmic death rate has been reported in patients with coronary heart disease (CHD). Sodium channel blockers should prevent initiation of reentry activation by reducing directional differences in cardiac conduction (anisotropy). However, in vitro data demonstrated, that reduction of membrane excitability, e.g. by lowering the inward Na+ current, increases the risk for conduction failure and associated reentry arrhythmias. In 11 dogs the effects of myocardial ischemia, premature epicardial stimulation (PES) and propafenone on anisotropic conduction properties were tested using three-dimensional mapping techniques. The epicardial (longitudinal and transverse to fiber orientation) and transmural (oblique and straight) spread of activation was reconstructed during constant and PES. At baseline, conduction velocities (CV) were higher along (1.20 +/- 0.41 m/s) than across (0.91 +/- 0.19 m/s; p < 0.05) epicardial muscle fibers as well as along oblique (1.77 +/- 0.75 m/s) compared to straight (0.39 +/- 0.09 m/s, p < 0.05) transmural pathways. Acute ischemia did not significantly reduce tissue anisotropy. PES and additional administration of propafenone epicardially eliminated and transmurally profoundly reduced tissue anisotropy (longitudinal 0.58 +/- 0.09 m/s, transverse 0.69 +/- 0.08 m/s, oblique 0.69 +/- 0.28 m/s, straight 0.27 +/- 0.07 m/s). However, reduced anisotropy was associated with a higher probability for conduction block along myocardial fibers in the epicardium and along oblique transmural pathways. Our data show, that propafenone exhibits both potential pro- and antiarrhythmic effects in dogs with acute myocardial ischemia. These results possibly provide more insights in mechanisms underlying the excessive drug-associated arrhythmic death rate in patients with CHD.
Asunto(s)
Antiarrítmicos/farmacología , Arritmias Cardíacas/fisiopatología , Corazón/fisiopatología , Isquemia Miocárdica/fisiopatología , Propafenona/farmacología , Animales , Anisotropía , Perros , Estimulación Eléctrica , Electrocardiografía/efectos de los fármacos , Sistema de Conducción Cardíaco/efectos de los fármacos , Pericardio/efectos de los fármacosRESUMEN
Controversy exists as to the homogeneity of repolarization throughout the canine ventricular wall in vivo. The type of anesthesia has been shown to affect regional differences in monophasic action potential duration and the inducibility of polymorphic ventricular tachycardias (PVTs) in normal canine hearts. This study was conducted to determine refractory patterns and arrhythmia susceptibility in relation to halothane or pentobarbital anesthesia in dogs with chronic atrioventricular block and biventricular hypertrophy. In 12 dogs with chronic atrioventricular block, 60 needle electrodes (12 mm long, four bipolar electrodes, interelectrode distance of 2 mm) were inserted into the left and right ventricle. Six dogs were anesthetized with pentobarbital and six with halothane. Effective refractory periods (ERPs) were determined along 14 randomly selected needles at baseline and after application of almokalant (0.34 mmol/kg) (basic cycle length 1,000 ms, extrastimulus technique). At baseline and on almokalant, ERPs were uniform, independent of the type of anesthesia. With halothane anesthesia, ERPs were significantly longer under both conditions. Almokalant induced not only a prolongation of ERP in both groups but also a significant increase in transmural dispersion of ERP and in maximum dispersion of ERP. However, local refractory gradients were not specific to any muscle layer and did not seem to be related to the occurrence of PVTs. Almokalant did not induce arrhythmias in any dog in the pentobarbital group, but in four of six animals in the halothane group, apparently due to the more marked prolongation in ERP. Independent of the type of anesthesia, hypertrophied hearts of dogs with chronic atrioventricular block exhibit uniform refractory patterns. Longer ERPs with a comparable degree of dispersion on halothane are associated with a high incidence of drug-induced PVTs, whereas shorter ERPs on pentobarbital seem to prevent arrhythmia induction.
Asunto(s)
Adyuvantes Anestésicos/toxicidad , Anestésicos por Inhalación/toxicidad , Halotano/toxicidad , Bloqueo Cardíaco/complicaciones , Pentobarbital/toxicidad , Taquicardia Ventricular/inducido químicamente , Animales , Antiarrítmicos/farmacología , Perros , Interacciones Farmacológicas , Femenino , Masculino , Propanolaminas/farmacología , Taquicardia Ventricular/complicacionesRESUMEN
In the MADIT study, a selected group of postinfarction patients with asymptomatic nonsustained ventricular tachycardia (NSVT) has been shown to benefit from prophylactic ICD treatment. The present study analyzed the variability of NSVT in a patient population fulfilling the non-invasive MADIT criteria. Three consecutive Holter ECGs were performed in weekly intervals in 68 postinfarction patients with an LVEF < or = 0.35. Patients with NSVT underwent programmed ventricular stimulation (PVS); patients were implanted with an ICD if sustained VT or VF was inducible. If NSVT was found in at least two recordings, the arrhythmia was defined as reproducible. In 28 (41%) of the 68 patients, NSVT was found in at least one recording. Seventeen patients revealed NSVT in the first, the remaining 11 in the second registration; no patient had NSVT only in the third Holter. Of the patients with NSVT, 50% had only one, 39% had two, and 11% had three positive recordings. Thus, reproducible NSVT was found in only 50% of the patients with NSVT. Predictors for reproducibility were LVEF > 0.27, NYHA Class I, absence of digitalis therapy, and > 2 NSVT per 24-hour period. Reproducible NSVT was not associated with risk factors such as elevated mean heart rate, reduced heart rate variability, late potentials, or inducibility of sustained VT during PVS. During 17 +/- 9 months of follow-up, seven (10%) patients experienced arrhythmic events: two without and five with previously documented NSVT. In the latter patients, first occurrence of NSVT was consistently in the first Holter; only two of them had reproducible NSVT. In postinfarction patients, the risk factor NSVT exhibits marked spontaneous variability, especially in those with a low number of NSVT per 24-hour period, LVEF < 0.27 or NYHA III, which limits its clinical value as a selection criterion for PVS. Reproducibility of NSVT itself does not seem to be an independent risk factor.
Asunto(s)
Electrocardiografía Ambulatoria , Taquicardia Ventricular/diagnóstico , Muerte Súbita Cardíaca , Desfibriladores Implantables , Electrocardiografía , Técnicas Electrofisiológicas Cardíacas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Reproducibilidad de los Resultados , Factores de RiesgoRESUMEN
Recent in vitro studies have described regional differences of ion current expression and function, possibly accounting for reduced homogeneity of repolarization in the heart. In 11 intact canine hearts regional disparity of repolarization was determined at baseline and after administration of the I(Kr) blocking agent dofetilide (30 microg/kg) and the I(Ks)-blocking agent chromanol 293b (10 mg/kg). Effective refractory periods (ERPs) were determined through up to 10 needle electrodes inserted into basal, midwall and apical regions of the left ventricular wall using the extrastimulus technique (cycle length [CL] 300 and 850 ms). At baseline (CL of 850 ms), ERPs were significantly longer in epicardial muscle layers of the apex compared to the base. In deeper muscle layers regional differences of ERPs were not detectable. Administration of dofetilide increased apico-basal disparity of repolarization, due to a more marked increase of ERPs in the apex than in the base. In contrast, homogeneous ERPs were evident along the apico-basal axis after administration of chromanol 293b. Transmural dispersion of refractoriness could not be observed in any region at baseline, or after drug-administration. In the intact canine heart, apico-basal disparity of repolarization varies between individual muscle layers. Dependent on their current specificity, antiarrhythmic agents may enhance or diminish regional disparity of repolarization.
Asunto(s)
Antiarrítmicos/farmacología , Cromanos/farmacología , Fenetilaminas/farmacología , Bloqueadores de los Canales de Potasio/farmacología , Canales de Potasio de Rectificación Interna/antagonistas & inhibidores , Sulfonamidas/farmacología , Función Ventricular Izquierda/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Estimulación Cardíaca Artificial , Ablación por Catéter , Perros , Electrofisiología , Ventrículos Cardíacos/efectos de los fármacos , Miocardio/metabolismo , Pericardio/metabolismo , Función Ventricular , Función Ventricular Izquierda/fisiologíaRESUMEN
BACKGROUND: Dogs with chronic AV block exposed to type-III antiarrhythmic agents develop polymorphic ventricular tachycardias (PVT). Controversy exists regarding PVT mechanism and underlying pathophysiology. METHODS AND RESULTS: In dogs with acute (n = 10, AAVB) or chronic AV block (n = 14, CAVB, 62 +/- 5 days after AV-node ablation) 60 pins (12 mm long, 4 bipolar electrodes) were inserted into both ventricles. QT intervals and effective refractory periods (ERP) at 56 +/- 22 randomly selected sites (extrastimulus technique, 800 ms basic cycle length) were determined before and after Almokalant (0.34 micromol/kg). A multiplexer mapping system was used to reconstruct 3D activation patterns. The heart-to-body-weight index (HBWI) was obtained after the experiments. CAVB led to a significant increase in HBWI (11.3 +/- 1.5 vs. 9 +/- 1.2 g/kg BW, p < 0.001), and a significant increase in ERP (280 +/- 28 ms vs. 260 +/- 37 ms, p < 0.05) and QT interval (339 +/- 16 vs. 288 +/-12 ms, p < 0.05). Dispersion (DISP) of ERP was similar for AAVB and CAVB dogs. No AAVB dog, but 9 of 14 CAVB dogs developed PVTs in response to Almokalant. All PVTs originated from an endocardial focus. Consecutive beats continued to reveal centrifugal activation patterns in 8 of 10 episodes. In only 2 episodes was reentrant activation evident. CONCLUSION: Myocardial hypertrophy associated with CAVB predisposes the canine heart to drug induced PVTs. This seems to be primarily linked to prolonged repolarization. PVTs in this model are not only initiated, but also perpetuated by a centrifugal spread of activation.
Asunto(s)
Antiarrítmicos/efectos adversos , Sistema de Conducción Cardíaco/fisiopatología , Propanolaminas/efectos adversos , Torsades de Pointes/inducido químicamente , Torsades de Pointes/fisiopatología , Animales , Cardiomegalia/complicaciones , Cardiomegalia/fisiopatología , Perros , Electrocardiografía , Bloqueo Cardíaco/complicaciones , Bloqueo Cardíaco/fisiopatología , Modelos AnimalesRESUMEN
Chronic atrioventricular (AV) block (CAVB) and biventricular hypertrophy in dogs increase susceptibility to drug-induced polymorphic ventricular tachycardia (PVT). In various rodent models, cyclosporin A (CsA) prevented hypertrophy. A similar effect in the CAVB model would allow us to determine whether hypertrophy represents an epiphenomenon, the cause of electrophysiological changes, and/or the anatomic substrate for PVTs. Upon AV node ablation, 6 dogs were studied acutely (AAVB), 25 dogs were kept for 6 (6W) and 12 wk (12W), receiving no treatment [CTL-CAVB-6W (n=6) and CTL-CAVB-12W (n=7)] or a daily oral dose of 10-20 mg/kg CsA directly (n=6, CsA-CAVB-6W) or 6 wk after radio-frequency ablation (n=6, CsA-CAVB-12W). For the final study, dogs were anesthetized, and 60 needles were inserted into both ventricles and connected to a multiplexer mapping system. Local effective refractory periods (ERPs) were determined at 56 +/- 22 randomly selected sites (extrastimulus technique, basic cycle length=800 ms). Arrhythmias within 30 min after application of almokalant (0.34 micromol/kg iv) were registered. The hearts were then excised to obtain the heart weight-body weight index (HBWI). Compared with AAVB, CTL-CAVB-6W and CTL-CAVB-12W showed increased HBWI and ERP associated with PVT inducibility in none of six AAVB dogs, four of six CTL-CAVB-6W dogs, and one of seven CTL-CAVB-12W dogs. Compared with CTL-CAVB-6W and CTL-CAVB-12W, CsA-CAVB-6W and CsA-CAVB-12W partially prevented hypertrophy or led to a regression of hypertrophy without reducing ERP prolongation. Despite ERP prolongation, PVTs were no longer inducible with CsA treatment. Thus prolongation of refractoriness seems to provide the trigger, but hypertrophy provides the essential substrate for the induction of PVTs in this model.