RESUMO
BACKGROUND: We conducted a multicenter study to evaluate mapping and ablation of ventricular fibrillation (VF) substrates or VF triggers in early repolarization syndromes (ERS) or J-wave syndrome (JWS). METHODS: We studied 52 patients with ERS (4 women; median age, 35 years) with recurrent VF episodes. Body surface electrocardiographic imaging and endocardial and epicardial electroanatomical mapping of both ventricles were performed during sinus rhythm and VF for localization of triggers, substrates, and drivers. Ablations were performed on VF substrates, defined as areas that had late depolarization abnormalities characterized by low-voltage fractionated late potentials, and VF triggers. RESULTS: Fifty-one of the 52 patients had detailed mapping that revealed 2 phenotypes: group 1 had late depolarization abnormalities predominantly at the right ventricular (RV) epicardium (n=40), and group 2 had no depolarization abnormalities (n=11). Group 1 can be subcategorized into 2 groups: Group 1A included 33 patients with ERS with Brugada electrocardiographic pattern, and group 1B included 7 patients with ERS without Brugada electrocardiographic pattern. Late depolarization areas colocalize with VF driver areas. The anterior RV outflow tract/RV epicardium and the RV inferior epicardium are the major substrate sites for group 1. The Purkinje network is the leading underlying VF trigger in group 2 that had no substrates. Ablations were performed in 43 patients: 31 and 5 group 1 patients had only VF substrate ablation and VF substrates plus VF trigger, respectively (mean, 1.4±0.6 sessions); 6 group 2 patients and 1 patient without group classification had only Purkinje VF trigger ablation (mean, 1.2±0.4 sessions). Ablations were successful in reducing VF recurrences (P<0.0001). After follow-up of 31±26 months, 39 (91%) had no VF recurrences. CONCLUSIONS: There are 2 phenotypes of ERS/J-wave syndrome: one with late depolarization abnormality as the underlying mechanism of high-amplitude J-wave elevation that predominantly resides in the RV outflow tract and RV inferolateral epicardium, serving as an excellent target for ablation, and the other with pure ERS devoid of VF substrates but with VF triggers that are associated with Purkinje sites. Ablation is effective in treating symptomatic patients with ERS/J-wave syndrome with frequent VF episodes.
Assuntos
Síndrome de Brugada/fisiopatologia , Endocárdio/fisiopatologia , Taquicardia Ventricular/fisiopatologia , Fibrilação Ventricular/fisiopatologia , Adulto , Ablação por Cateter/métodos , Eletrocardiografia/métodos , Técnicas Eletrofisiológicas Cardíacas/métodos , Mapeamento Epicárdico/métodos , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Early repolarization indicates a distinct electrocardiographic phenotype affecting the junction between the QRS complex and the ST segment in inferolateral leads (inferolateral J-wave syndromes). It has been considered a benign electrocardiographic variant for decades, but recent clinical studies have demonstrated its arrhythmogenicity in a small subset, supported by experimental studies showing transmural dispersion of repolarization. Here we review the current knowledge and the issues of risk stratification that limit clinical management. In addition, we report on new mapping data of patients refractory to pharmacologic treatment using high-density electrogram mapping at the time of inscription of J wave. These data demonstrate that distinct substrates, delayed depolarization, and abnormal early repolarization underlie inferolateral J-wave syndromes, with significant implications. Finally, based on these data, we propose a new simplified mechanistic classification of sudden cardiac deaths without apparent structural heart disease.
Assuntos
Arritmias Cardíacas , Morte Súbita Cardíaca , Eletrocardiografia/métodos , Técnicas Eletrofisiológicas Cardíacas/métodos , Arritmias Cardíacas/complicações , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Medição de RiscoRESUMO
BACKGROUND: Sudden cardiac death because of ventricular fibrillation (VF) is commonly unexplained in younger victims. Detailed electrophysiological mapping in such patients has not been reported. METHODS: We evaluated 24 patients (29±13 years) who survived idiopathic VF. First, we used multielectrode body surface recordings to identify the drivers maintaining VF. Then, we analyzed electrograms in the driver regions using endocardial and epicardial catheter mapping during sinus rhythm. Established electrogram criteria were used to identify the presence of structural alterations. RESULTS: VF occurred spontaneously in 3 patients and was induced in 16, whereas VF was noninducible in 5. VF mapping demonstrated reentrant and focal activities (87% versus 13%, respectively) in all. The activities were dominant in one ventricle in 9 patients, whereas they had biventricular distribution in others. During sinus rhythm areas of abnormal electrograms were identified in 15/24 patients (62.5%) revealing localized structural alterations: in the right ventricle in 11, the left ventricle in 1, and both in 3. They covered a limited surface (13±6 cm2) representing 5±3% of the total surface and were recorded predominantly on the epicardium. Seventy-six percent of these areas were colocated with VF drivers (P<0.001). In the 9 patients without structural alteration, we observed a high incidence of Purkinje triggers (7/9 versus 4/15, P=0.033). Catheter ablation resulted in arrhythmia-free outcome in 15/18 patients at 17±11 months follow-up. CONCLUSIONS: This study shows that localized structural alterations underlie a significant subset of previously unexplained sudden cardiac death. In the other subset, Purkinje electrical pathology seems as a dominant mechanism.
Assuntos
Potenciais de Ação , Morte Súbita Cardíaca/etiologia , Técnicas Eletrofisiológicas Cardíacas , Frequência Cardíaca , Ramos Subendocárdicos/fisiopatologia , Fibrilação Ventricular/diagnóstico , Adolescente , Adulto , Estimulação Cardíaca Artificial , Ablação por Cateter , Causas de Morte , Morte Súbita Cardíaca/prevenção & controle , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Ramos Subendocárdicos/cirurgia , Fatores de Risco , Fatores de Tempo , Fibrilação Ventricular/complicações , Fibrilação Ventricular/fisiopatologia , Fibrilação Ventricular/prevenção & controle , Adulto JovemRESUMO
BACKGROUND: The repolarization pattern of the human heart is unknown. OBJECTIVE: The purpose of this study was to perform a multisite analysis of the activation-repolarization patterns and mRNA expression patterns of ion channel subunits in isolated human hearts. METHODS: Hearts from 3 donors without reported cardiac disease were Langendorff perfused with the patient's own blood. A standard ECG was obtained before explantation. Up to 92 unipolar electrograms from 24 transmural needles were obtained during right atrial pacing. Local activation and repolarization times and activation-recovery intervals (ARI) were measured. The mRNA levels of subunits of the channels carrying the transient outward current and slow and rapid components of the delayed rectifier current were determined by quantitative reverse transcriptase polymerase chain reaction at up to 63 sites. RESULTS: The repolarization gradients in the 3 hearts were different and occurred along all axes without midmural late repolarization. A negative activation-repolarization relationship occurred along the epicardium, but this relationship was positive in the whole hearts. Coefficients of variation of mRNA levels (40%-80%) and of the Kv7.1 protein (alpha-subunit slow delayed rectifier channel) were larger than those of ARIs (7%-17%). The regional mRNA expression patterns were similar in the 3 hearts, unlike the ARI profiles. The expression level of individual mRNAs and of Kv7.1 did not correlate with local ARIs at the same sites. CONCLUSION: In the normal human heart, repolarization gradients encompass all axes, without late midmural repolarization. Last activated areas do not repolarize first as previously assumed. Gradients of mRNAs of single ion channel subunits and of ARIs do not correlate.
Assuntos
Coração , Canal de Potássio KCNQ1/metabolismo , Potenciais de Ação/fisiologia , Técnicas Eletrofisiológicas Cardíacas/métodos , Coração/fisiologia , Coração/fisiopatologia , Humanos , Período Refratário Eletrofisiológico/fisiologia , Projetos de PesquisaAssuntos
Arritmias Cardíacas , Técnicas Eletrofisiológicas Cardíacas/métodos , Ventrículos do Coração , Coração/crescimento & desenvolvimento , Animais , Arritmias Cardíacas/embriologia , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Fenômenos Eletrofisiológicos , Ventrículos do Coração/embriologia , Ventrículos do Coração/crescimento & desenvolvimento , Ventrículos do Coração/fisiopatologia , HumanosRESUMO
BACKGROUND: Brugada syndrome (BrS) is characterized by a typical ECG pattern. We aimed to determine the pathophysiologic basis of the ST-segment in the BrS-ECG with data from various epicardial and endocardial right ventricular activation mapping procedures in 6 BrS patients and in 5 non-BrS controls. METHODS AND RESULTS: In 7 patients (2 BrS and 5 controls) with atrial fibrillation, an epicardial 8×6 electrode grid (interelectrode distance 1 mm) was placed epicardially on the right ventricular outflow tract (RVOT) before video-assisted thoracoscopic surgical pulmonary vein isolation. In 2 other BrS patients, endocardial, epicardial RV (CARTO), and body surface mapping was performed. In 2 additional BrS patients, we performed decremental preexcitation of the RVOT before endocardial RV mapping. During video-assisted thoracoscopic surgical pulmonary vein isolation and CARTO mapping, BrS patients (n=4) showed greater activation delay and more fractionated electrograms in the RVOT region than controls. Ajmaline administration increased the region with fractionated electrograms, as well as ST-segment elevation. Preexcitation of the RVOT (n=2) resulted in ECGs that supported the current-to-load mismatch hypothesis for ST-segment elevation. Body surface mapping showed that the area with ST-segment elevation anatomically correlated with the area of fractionated electrograms and activation delay at the RVOT epicardium. CONCLUSIONS: ST-segment elevation and epicardial fractionation/conduction delay in BrS patients are most likely related to the same structural subepicardial abnormalities, but the mechanism is different. ST-segment elevation may be caused by current-to-load mismatch, whereas fractionated electrograms and conduction delay are expected to be caused by discontinuous conduction in the same area with abnormal myocardium.
Assuntos
Fibrilação Atrial/diagnóstico , Síndrome de Brugada/diagnóstico , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Endocárdio/fisiopatologia , Pericárdio/fisiopatologia , Função Ventricular Direita , Potenciais de Ação , Adulto , Idoso , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Mapeamento Potencial de Superfície Corporal , Síndrome de Brugada/fisiopatologia , Estudos de Casos e Controles , Ablação por Cateter/métodos , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Veias Pulmonares/fisiopatologia , Veias Pulmonares/cirurgia , Cirurgia Torácica VídeoassistidaRESUMO
BACKGROUND: Initiation of reentrant ventricular tachycardia (VT) involves complex interactions between front and tail of the activation wave. Recent experimental work has identified the time interval between S2 repolarization proximal to a line of functional block and S2 activation at the adjacent distal side as a critical determinant of reentry. OBJECTIVES: We hypothesized that (1) an algorithm could be developed to generate a spatial map of this interval ("reentry vulnerability index" [RVI]), (2) this would accurately identify a site of reentry without the need to actually induce the arrhythmia, and (3) it would be possible to generate an RVI map in patients during routine clinical procedures. METHODS: An algorithm was developed that calculated RVI between all pairs of electrodes within a given radius. RESULTS: The algorithm successfully identified the region with increased susceptibility to reentry in an established Langendorff pig heart model and the site of reentry and rotor formation in an optically mapped sheep ventricular preparation and computational simulations. The feasibility of RVI mapping was evaluated during a clinical procedure by coregistering with cardiac anatomy and physiology of a patient undergoing VT ablation. CONCLUSION: We developed an algorithm to calculate a reentry vulnerability index from intervals between local repolarization and activation. The algorithm accurately identified the region of reentry in 2 animal models of functional reentry. The clinical application was demonstrated in a patient with VT and identified the area of reentry without the need of inducing the arrhythmia.
Assuntos
Algoritmos , Sistema de Condução Cardíaco/fisiopatologia , Taquicardia Ventricular , Animais , Simulação por Computador , Suscetibilidade a Doenças/diagnóstico , Suscetibilidade a Doenças/fisiopatologia , Eletrocardiografia/métodos , Técnicas Eletrofisiológicas Cardíacas/métodos , Humanos , Modelos Animais , Modelos Cardiovasculares , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Ovinos , Suínos , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologiaRESUMO
BACKGROUND: In patients with atrial fibrillation (AF), the autonomic nervous system is supposed to play an role in triggering AF; however, little is known of the effect on atrial conduction characteristics. OBJECTIVE: The purpose of this study was to study the effect of ganglionic plexus (GP) stimulation during sinus rhythm on atrial and pulmonary vein conduction in patients during thoracoscopic surgery for AF METHODS: In 25 patients, the anterior right ganglionic plexus (ARGP) was stimulated (16 Hz, at 1, 2, and 5 mA). Epicardial electrograms were recorded using a 48-electrode map from the right pulmonary vein (RPV) or right atrial (RA). Intra-atrial activation time (IAT), local activation time (LAT), and inhomogeneity of conduction (IIC) were determined. ECG parameters (P-P, P-R interval) were measured. RESULTS: P-P interval was 956 ± 157 ms (range 768-1368 ms), and P-R interval was 203 ± 37 ms (range 136-280 ms). After ARGP stimulation, a short-lasting increase of P-P interval was observed, more prominent at higher output (1 mA = 82 ms, 2 mA = 180 ms, 5 mA = 268 ms, all P <.01 vs baseline). P-R interval remained unchanged. IAT was 34.4 ms (range 5.6-50.3 ms) at the RA and 105.8 ms (range 79.7-163.3 ms) at the RPV. After 1-mA stimulation IAT increased, in patients taking beta-blockers (P = .001), or it decreased, and this change persisted after subsequent stimulation at higher current (1 mA, P = .001; 2 mA, P = .401; 5 mA, P = .593). Similar changes were observed for LAT and IIC. CONCLUSION: ARGP stimulation results in a short-lasting, output-dependent decrease in sinus node frequency due to a parasympathetic response. Stimulation of the ARGP induced a prolonged increase or decrease in conduction characteristics in patients with AF, consistent with a persistent differential parasympathetic and/or sympathetic response.
Assuntos
Fibrilação Atrial/terapia , Estimulação Elétrica/métodos , Técnicas Eletrofisiológicas Cardíacas/métodos , Gânglios Autônomos/fisiopatologia , Átrios do Coração/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Nó Sinoatrial/fisiopatologia , Idoso , Fibrilação Atrial/fisiopatologia , Função do Átrio Esquerdo , Eletrocardiografia , Feminino , Átrios do Coração/inervação , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: The genesis of the electrocardiographic T wave is incompletely understood and subject to controversy. We have correlated the ventricular repolarization sequence with simultaneously recorded T waves. METHODS AND RESULTS: Nine pig hearts were Langendorff-perfused (atrial pacing, cycle length 650 ms). Local activation and repolarization times were derived from unipolar electrograms sampling the ventricular myocardium. Dispersion of repolarization time was determined along 4 anatomic axes: left ventricle (LV)-right ventricle (RV), LV:apico-basal, LV:anterior-posterior, and LV:transmural. The heart was immersed in a fluid-filled bucket containing 61 electrodes to determine Tp (Tpeak in lead of maximum integral), TpTe (Tp to Tend), and TpTe_total (first Tpeak in any lead to last Tend in any lead). Repolarization was nonlinearly distributed in time. RT25 (time at which 25% of sites were repolarized, 288±26 ms) concurred with Tp. TpTe was 38±8 ms, and TpTe_total was 75±9 ms. TpTe_total correlated with dispersion of repolarization time in the entire heart (73±18 ms), but not with dispersion of repolarization times along individual axes (LV-RV, 66±17 ms; LV:apico-basal, 51±18 ms; LV:anterior-posterior, 51±27 ms; mean LV:transmural, 14±7 ms; all n=9). CONCLUSIONS: We provide a correlation between local repolarization and T wave in a pseudo-ECG. Repolarization differences along all anatomic axes contribute to the T wave. TpTe_total represents total dispersion of repolarization. At Tp, ≈25% of ventricular sites have been repolarized.
Assuntos
Potenciais de Ação/fisiologia , Eletrocardiografia , Sistema de Condução Cardíaco/fisiologia , Função Ventricular/fisiologia , Animais , Eletrodos Implantados , Técnicas Eletrofisiológicas Cardíacas , Coração/fisiologia , Humanos , Masculino , Modelos Animais , Tempo de Reação , Sensibilidade e Especificidade , SuínosRESUMO
BACKGROUND: During heart failure (HF), cardiac metabolic substrate preference changes from fatty acid (FA) toward glucose oxidation. This change may cause progression toward heart failure. We hypothesize that a diet rich in FAs may prevent this process, and that dietary ω3-FAs have an added antiarrhythmic effect based on action potential (AP) shortening in animals with HF. METHODS AND RESULTS: Rabbits were fed a diet containing 1.25% (w/w) high oleic sunflower oil (HF-ω9, N=11), 1.25% fish oil (HF-ω3, N=11), or no supplement (HF-control, N=8). Subsequently, HF was induced by volume and pressure overload. After 4 months, HF-parameters were assessed, electrocardiograms were recorded, and blood and ventricular tissue were collected. Myocytes were isolated for patch clamp or intracellular Ca(2+)- recordings to study electrophysiologic remodeling and arrhythmogenesis. Both the HF-ω9 and the HF-ω3 groups had larger myocardial FA oxidation capacity than HF control. The HF-ω3 group had significantly lower mean (± SEM) relative heart and lung weight (3.3±0.13 and 3.2±0.12 g kg(-1), respectively) than HF control (4.8±0.30 and 4.5±0.23), and shorter QTc intervals (167±2.6 versus 182±6.4). The HF-ω9 also displayed a significantly reduced relative heart weight (3.6±0.26), but had similar QTc (179±4.3) compared with HF control. AP duration in the HF-ω3 group was ≈20% shorter due to increased I(to1) and I(K1) and triggered activity, and Ca(2+)-aftertransients were less than in the HF-ω9 group. CONCLUSIONS: Dietary unsaturated FAs started prior to induction of HF prevent hypertrophy and HF. In addition, fish oil FAs prevent HF-induced electrophysiologic remodeling and arrhythmias.
Assuntos
Arritmias Cardíacas/prevenção & controle , Cardiomegalia/prevenção & controle , Gorduras Insaturadas na Dieta/uso terapêutico , Ácidos Graxos Insaturados/uso terapêutico , Insuficiência Cardíaca/prevenção & controle , Insuficiência Cardíaca/fisiopatologia , Potenciais de Ação/fisiologia , Administração Oral , Animais , Arritmias Cardíacas/patologia , Arritmias Cardíacas/fisiopatologia , Cálcio/metabolismo , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Gorduras Insaturadas na Dieta/administração & dosagem , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Ácidos Graxos Insaturados/administração & dosagem , Insuficiência Cardíaca/patologia , Masculino , Modelos Animais , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Técnicas de Patch-Clamp , CoelhosRESUMO
Increased consumption of fatty fish, rich in omega-3-polyunsaturated fatty acids (ω3-PUFAs) reduces the severity and number of arrhythmias. Long-term ω3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating ω3-PUFAs in the bloodstream and incorporated ω3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating ω3-PUFAs in the bloodstream enhance or diminish the effects of incorporated ω3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (ω3) or sunflower oil (ω9, as control) for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch-clamp technique in the absence and presence of acutely administered ω3-PUFAs. Plasma of ω3 fed rabbits contained more free eicosapentaenoic acid (EPA) and isolated myocytes of ω3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA) in their sarcolemma compared to control. In the absence of acutely administered fatty acids, ω3 myocytes had a shorter action potential with a more negative plateau than ω9 myocytes. In the ω9 myocytes, but not in the ω3 myocytes, acute administration of a mixture of EPA + DHA shortened the action potential significantly. From these data we conclude that incorporated ω3-PUFAs into the sarcolemma and acutely administered ω3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac ω3-PUFA status will probably not benefit from short term ω3 supplementation as an antiarrhythmic therapy.
RESUMO
BACKGROUND: The Brugada sign has been associated with mutations in SCN5A and with right ventricular structural abnormalities. Their role in the Brugada sign and the associated ventricular arrhythmias is unknown. OBJECTIVE: The purpose of this study was to delineate the role of structural abnormalities and sodium channel dysfunction in the Brugada sign. METHODS: Activation and repolarization characteristics of the explanted heart of a patient with a loss-of-function mutation in SCN5A (G752R) and dilated cardiomyopathy were determined after induction of right-sided ST-segment elevation by ajmaline. In addition, right ventricular structural discontinuities and sodium channel dysfunction were simulated in a computer model encompassing the heart and thorax. RESULTS: In the explanted heart, disappearance of local activation in unipolar electrograms at the basal right ventricular epicardium was followed by monophasic ST-segment elevation. The local origin of this phenomenon was confirmed by coaxial electrograms. Neither early repolarization nor late activation correlated with ST-segment elevation. At sites of local ST-segment elevation, the subepicardium was interspersed with adipose tissue and contained more fibrous tissue than either the left ventricle or control hearts. In computer simulations entailing right ventricular structural discontinuities, reduction of sodium channel conductance or size of the gaps between introduced barriers resulted in subepicardial excitation failure or delayed activation by current-to-load mismatch and in the Brugada sign on the ECG. CONCLUSION: Right ventricular excitation failure and activation delay by current-to-load mismatch in the subepicardium can cause the Brugada sign. Therefore, current-to-load mismatch may underlie the ventricular arrhythmias in patients with the Brugada sign.
Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Disfunção Ventricular Direita/fisiopatologia , Adolescente , Ajmalina , Antiarrítmicos , Síndrome de Brugada/genética , Síndrome de Brugada/fisiopatologia , Cardiomiopatia Dilatada/genética , Cromatografia Líquida de Alta Pressão , Simulação por Computador , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Feminino , Predisposição Genética para Doença , Transplante de Coração , Humanos , Técnicas In Vitro , Lamina Tipo A/genética , Proteínas Musculares/genética , Mutação , Canal de Sódio Disparado por Voltagem NAV1.5 , Canais de Sódio/genética , Disfunção Ventricular Direita/genéticaRESUMO
BACKGROUND: The relation between induction of arrhythmias and dispersion of repolarization is not completely understood. OBJECTIVE: The purpose of this study was to study the relation between heterogeneity in repolarization and arrhythmogenesis under conditions of selective regional action potential prolongation and shortening. METHODS: Pig hearts were perfused in a Langendorff setup. The left anterior descending artery (LAD) was cannulated and perfused. Sotalol (220 microM) was infused in the aortic cannula, and pinacidil (20 microM) was infused through the LAD, causing a gradient in repolarization time between the two myocardial regions. Premature stimulation was performed from the LAD region. RESULTS: No transmural repolarization gradients developed after infusion of the drugs. High-density epicardial activation/repolarization mapping (176 unipolar electrodes, 2-mm interelectrode spacing) revealed a maximum repolarization gradient of approximately 120 ms over 14 mm. The critical parameter for differentiating between the occurrence of reentry and the mere occurrence of a line of activation block between the two myocardial regions (and no reentry) was not the magnitude of the repolarization gradient but the timing of arrival of the premature activation wave at the distal side of the line of activation block relative to the repolarization time of the premature beat proximal to the line of block. No spontaneous arrhythmias were observed despite the presence of the repolarization gradient. CONCLUSION: It is not the repolarization gradient but the restitution characteristics of the tissue with the shorter action potential, in combination with the time of arrival of the premature wavefront at the distal side of the line of block, that determines the occurrence of reentry.
Assuntos
Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Pinacidil/farmacologia , Sotalol/farmacologia , Potenciais de Ação/fisiologia , Animais , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Sistema de Condução Cardíaco/efeitos dos fármacos , SuínosRESUMO
Omega-3 polyunsaturated fatty acids (omega 3-PUFAs) from fish oil modulate various ion channels, including the L-type calcium current (I(Ca,L)). As a result, fish oil shortens the cardiac action potential and may cause a loss of the dome of the action potential (AP). Under conditions of increased preexisting heterogeneity in repolarization this may aggravate dispersion in action potential duration. We isolated ventricular myocytes of explanted hearts from patients with cardiomyopathy at the time of cardiac transplantation, and characterized spike-and-dome morphology in the presence of acutely administered fish oil. Fish oil omega 3-PUFA eicosapentaenoic acid (EPA), but not the control omega 9-PUFA oleic acid (OA), curtails the AP-dome in a heterogeneous manner and may even result in loss of the AP-dome in some but not all myocytes.
Assuntos
Potenciais de Ação/efeitos dos fármacos , Arritmias Cardíacas/prevenção & controle , Ácido Eicosapentaenoico/uso terapêutico , Miócitos Cardíacos/efeitos dos fármacos , Idoso , Ácido Eicosapentaenoico/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/citologia , Miocárdio/metabolismo , Miócitos Cardíacos/fisiologia , PerfusãoRESUMO
Very long-chain n-3 PUFA from fish are suggested to play a role in the development of the brain. Fish oil feeding results in higher proportions of n-3 PUFA in the brains of newborn piglets. However, the effect of fish oil on the fatty acid composition of specific cerebral brain lobes in juvenile pigs is largely uninvestigated. This study examined the effect of a fish oil diet on the fatty acid composition of the frontal, parietal, temporal and occipital brain lobes in juvenile pigs (7 weeks old). Pigs were randomly allocated to a semipurified pig diet containing either 4% (w/w) fish oil (n 19) or 4% (w/w) high-oleic acid sunflower oil (HOSF diet, n 18) for a period of 8 weeks. The fish oil diet resulted in significantly higher proportions (%) of DHA in the frontal (10.6 (SD1.2)), parietal (10.2 (SD1.5)) and occipital brain lobes (9.9 (SD 1.3)), but not in the temporal lobe (7.7 (SD1.6)), compared with pigs fed the HOSF diet (frontal lobe, 7.5 (SD1.0); parietal lobe, 8.1 (SD 1.3); occipital lobe, 7.3 (SD1.2), temporal lobe, 6.6 (SD1.2). Moreover, the proportion of DHA was significantly lower in the temporal lobe compared with the frontal, parietal and occipital brain lobes in pigs fed a fish oil diet. In conclusion, the brains of juvenile pigs appear to be responsive to dietary fish oil, although the temporal brain lobe is less responsive compared with the other three brain lobes. The functional consequences of these differences are a challenging focus for future investigation.
Assuntos
Encéfalo/metabolismo , Gorduras na Dieta/administração & dosagem , Ácidos Graxos Ômega-3/administração & dosagem , Óleos de Peixe , Suínos/metabolismo , Ração Animal , Animais , Ácidos Graxos Ômega-3/análise , Ácidos Graxos Ômega-6/administração & dosagem , Ácidos Graxos Ômega-6/análise , Lobo Frontal/química , Masculino , Lobo Occipital/química , Lobo Parietal/química , Óleos de Plantas/administração & dosagem , Distribuição Aleatória , Óleo de Girassol , Lobo Temporal/químicaRESUMO
BACKGROUND: Fish oil reduces sudden death in patients with prior myocardial infarction. Sudden death in heart failure may be due to triggered activity based on disturbed calcium handling. We hypothesized that superfusion with omega3-polyunsaturated fatty acids (omega3-PUFAs) from fish inhibits triggered activity in heart failure. METHODS AND RESULTS: Ventricular myocytes were isolated from explanted hearts of rabbits with volume- and pressure-overload-induced heart failure and of patients with end-stage heart failure. Membrane potentials (patch-clamp technique) and intracellular calcium (indo-1 fluorescence) were recorded after 5 minutes of superfusion with Tyrode's solution (control), omega-9 monounsaturated fatty acid oleic acid (20 micromol/L), or omega3-PUFAs (docosahexaenoic acid or eicosapentaenoic acid 20 micromol/L). omega3-PUFAs shortened the action potential at low stimulation frequencies and caused an approximately 25% decrease in diastolic and systolic calcium (all P<0.05). Subsequently, noradrenalin and rapid pacing were used to evoke triggered activity, delayed afterdepolarizations, and calcium aftertransients. omega3-PUFAs abolished triggered activity and reduced the number of delayed afterdepolarizations and calcium aftertransients compared with control and oleic acid. Omega3-PUFAs reduced action potential shortening and intracellular calcium elevation in response to noradrenalin. Results from human myocytes were in accordance with the findings obtained in rabbit myocytes. CONCLUSIONS: Superfusion with omega3-PUFAs from fish inhibits triggered arrhythmias in myocytes from rabbits and patients with heart failure by lowering intracellular calcium and reducing the response to noradrenalin.
Assuntos
Óleos de Peixe/farmacologia , Insuficiência Cardíaca/patologia , Células Musculares/efeitos dos fármacos , Potenciais de Ação , Animais , Arritmias Cardíacas/prevenção & controle , Cálcio/análise , Células Cultivadas , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Insaturados/farmacologia , Humanos , Potenciais da Membrana , Células Musculares/citologia , Norepinefrina/farmacologia , CoelhosRESUMO
BACKGROUND: Brugada syndrome (BrS) is associated with lethal arrhythmias, which are linked to specific ST-segment changes (type-1 BrS-ECG) and the right ventricle (RV). The pathophysiological basis of the arrhythmias and type-1 BrS-ECG is unresolved. We studied the electrophysiological characteristics of the RV endocardium in BrS. METHODS AND RESULTS: RV endocardial electroanatomical mapping and stimulation studies were performed in controls (n=12) and BrS patients with a type-1 (BrS-1, n=10) or type-2 BrS-ECG (BrS-2, n=12) during the studies. BrS-1 patients had prominent impairment of RV endocardial impulse propagation when compared with controls, as represented by: (1) prolonged activation-duration during sinus rhythm (86+/-4 versus 65+/-3 ms), (2) increased electrogram fractionation (1.36+/-0.04 versus 1.15+/-0.01 deflections per electrogram), (3) longer electrogram duration (83+/-3 versus 63+/-2 ms), (4) activation delays on premature stimulation (longitudinal: 160+/-26 versus 86+/-9 ms; transversal: 112+/-5 versus 58+/-6 ms), and (5) abnormal transversal conduction velocity restitution (42+/-8 versus 18+/-2 ms increase in delay at shortest coupling intervals). Wider and more fractionated electrograms were also found in BrS-2 patients. Repolarization was not different between groups. CONCLUSIONS: BrS-1 and BrS-2 patients are characterized by wide and fractionated electrograms at the RV endocardium. BrS-1 patients display additional conduction slowing during sinus rhythm and premature stimulation along with abnormal transversal conduction velocity restitution. These patients may thus exhibit a substrate for slow and discontinuous conduction caused by abnormal active membrane processes and electric coupling. Our findings support the emerging notion that BrS is not solely attributable to abnormal electrophysiological properties but requires the conspiring effects of conduction slowing and tissue discontinuities.
Assuntos
Síndrome de Brugada/fisiopatologia , Estimulação Cardíaca Artificial , Técnicas Eletrofisiológicas Cardíacas , Endocárdio/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Potenciais de Ação , Adulto , Estudos de Casos e Controles , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Processamento de Sinais Assistido por ComputadorRESUMO
BACKGROUND: The concept that the interval between the peak (T(peak)) and the end (T(end)) of the T wave (T(p-e)) is a measure of transmural dispersion of repolarization time is widely accepted but has not been tested rigorously by transmural mapping of the intact heart. OBJECTIVES: The purpose of this study was to test the relationship of T(p-e) to transmural dispersion of repolarization by correlating local repolarization times at endocardial, midmural, and epicardial sites in the left and right ventricles with the T wave of the ECG. METHODS: Local activation times, activation-recovery intervals, and repolarization times were measured at 98 epicardial sites and up to 120 midmural and endocardial sites in eight open-chest dogs. In four of the dogs, long-term cardiac memory was induced by 3 weeks of ventricular pacing at 130 bpm because previous data suggest that, in this setting, delayed epicardial repolarization increases transmural dispersion. The other four dogs were sham operated. RESULTS: In sham dogs, T(p-e) was 41 +/- 2.2 ms (X +/- SEM), whereas the transmural dispersion of repolarization time was 2.7 +/- 4.2 ms (not significant between endocardium and epicardium). Cardiac memory was associated with evolution of a transmural gradient of 14.5 +/- 1.9 ms (P <.02), with epicardium repolarizing later than endocardium. The corresponding T(p-e) was 43 +/- 2.3 ms (not different from sham). In combined sham and memory dogs, T(p-e) intervals did not correlate with transmural dispersion of repolarization times. In contrast, dispersion of repolarization of the whole heart (measured as the difference between the earliest and the latest moment of repolarization from all left and right ventricular, endocardial, intramural, and epicardial recording sites) did correlate with T(p-e) (P <.0005, r = 0.98), although the latter underestimated total repolarization time by approximately 35%. The explanation for this finding is that parts of the heart fully repolarize before the moment of T(peak). CONCLUSION: T(p-e) does not correlate with transmural dispersion of repolarization but is an index of total dispersion of repolarization.