RESUMO
In this article, I show that the distribution of citations to papers published by the top 30 journals in the category Cardiac & Cardiovascular Systems of the Web of Science is extremely skewed. This skewness is to the right, which means that there is a long tail of papers that are cited much more frequently than the other papers of the same journal. The consequence is that there is a large difference between the mean and the median of the citation of the papers published by the journals. I further found that there are no differences between the citation distributions of the top 4 journals European Heart Journal, Circulation, Journal of the American College of Cardiology, and Circulation Research. Despite the fact that the journal impact factor (IF) varied between 23.425 for Eur Heart J and 15.211 for Circ Res with the other 2 journals in between, the median citation of their articles plus reviews (IF Median) was 10 for all 4 journals. Given the fact that their citation distributions were similar, it is obvious that an indicator (IF Median) that reflects this similarity must be superior to the classical journal impact factor, which may indicate a nonexisting difference. It is underscored that the IF Median is substantially lower than the journal impact factor for all 30 journals under consideration in this article. Finally, the IF Median has the additional advantage that there is no artificial ranking of 128 journals in the category but rather an attribution of journals to a limited number of classes with comparable impact.
Assuntos
Doenças Cardiovasculares , Sistema Cardiovascular , Fator de Impacto de Revistas , Publicações Periódicas como Assunto/normas , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/terapia , HumanosRESUMO
Skeletal myoblast (SkMB) transplantation has been conducted as a therapeutic strategy for severe heart failure. However, arrhythmogenicity following transplantation remains unsolved. We developed an in vitro model of myoblast transplantation with "patterned" or "randomly-mixed" co-culture of SkMBs and cardiomyocytes enabling subsequent electrophysiological, and arrhythmogenic evaluation. SkMBs were magnetically labeled with magnetite nanoparticles and co-cultured with neonatal rat ventricular myocytes (NRVMs) on multi-electrode arrays. SkMBs were patterned by a magnet beneath the arrays. Excitation synchronicity was evaluated by Ca(2+) imaging using a gene-encoded Ca(2+) indicator, G-CaMP2. In the monoculture of NRVMs (control), conduction was well-organized. In the randomly-mixed co-culture of NRVMs and SkMBs (random group), there was inhomogeneous conduction from multiple origins. In the "patterned" co-culture where an en bloc SKMB-layer was inserted into the NRVM-layer, excitation homogenously propagated although conduction was distorted by the SkMB-area. The 4-mm distance conduction time (CT) in the random group was significantly longer (197 ± 126 ms) than in control (17 ± 3 ms). In the patterned group, CT through NRVM-area did not change (25 ± 3 ms), although CT through the SkMB-area was significantly longer (132 ± 77 ms). The intervals between spontaneous excitation varied beat-to-beat in the random group, while regular beating was recorded in the control and patterned groups. Synchronized Ca(2+) transients of NRVMs were observed in the patterned group, whereas those in the random group were asynchronous. Patterned alignment of SkMBs is feasible with magnetic nanoparticles. Using the novel in vitro model mimicking cell transplantation, it may become possible to predict arrhythmogenicity due to heterogenous cell transplantation. J. Cell. Physiol. 231: 2249-2256, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Técnicas de Cocultura , Ventrículos do Coração/citologia , Nanopartículas de Magnetita/administração & dosagem , Mioblastos Esqueléticos/citologia , Miócitos Cardíacos/citologia , Animais , Arritmias Cardíacas/fisiopatologia , Células Cultivadas , Infarto do Miocárdio/fisiopatologia , Nanotecnologia/métodos , Ratos WistarAssuntos
Técnicas de Ablação , Potenciais de Ação , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/cirurgia , Eletrocardiografia , Sistema de Condução Cardíaco/cirurgia , Animais , Arritmias Cardíacas/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Humanos , Valor Preditivo dos TestesRESUMO
Spiral-wave (SW) reentry is a major organizing principle of ventricular tachycardia/fibrillation (VT/VF). We tested a hypothesis that pharmacological modification of gap junction (GJ) conductance affects the stability of SW reentry in a two-dimensional (2D) epicardial ventricular muscle layer prepared by endocardial cryoablation of Langendorff-perfused rabbit hearts. Action potential signals were recorded and analyzed by high-resolution optical mapping. Carbenoxolone (CBX; 30 µM) and rotigaptide (RG, 0.1 µM) were used to inhibit and enhance GJ coupling, respectively. CBX decreased the space constant (λ) by 36%, whereas RG increased it by 22-24% (n = 5; P < 0.01). During centrifugal propagation, there was a linear relationship between the wavefront curvature (κ) and local conduction velocity (LCV): LCV = LCV(0) - D·κ (D, diffusion coefficient; LCV(0), LCV at κ = 0). CBX decreased LCV(0) and D by 27 ± 3 and 57 ± 3%, respectively (n = 5; P < 0.01). RG increased LCV(0) and D by 18 ± 3 and 54 ± 5%, respectively (n = 5, P < 0.01). The regression lines with and without RG crossed, resulting in a paradoxical decrease of LCV with RG at κ > ~60 cm(-1). SW reentry induced after CBX was stable, and the incidence of sustained VTs (>30 s) increased from 38 ± 4 to 85 ± 4% after CBX (n = 18; P < 0.01). SW reentry induced after RG was characterized by decremental conduction near the rotation center, prominent drift and self-termination by collision with the anatomical boundaries, and the incidence of sustained VTs decreased from 40 ± 5 to 17 ± 6% after RG (n = 13; P < 0.05). These results suggest that decreased intercellular coupling stabilizes SW reentry in 2D cardiac muscle, whereas increased coupling facilitates its early self-termination.
Assuntos
Antiarrítmicos/farmacologia , Carbenoxolona/farmacologia , Comunicação Celular/efeitos dos fármacos , Junções Comunicantes/efeitos dos fármacos , Sistema de Condução Cardíaco/efeitos dos fármacos , Oligopeptídeos/farmacologia , Taquicardia Ventricular/prevenção & controle , Fibrilação Ventricular/prevenção & controle , Potenciais de Ação , Animais , Modelos Animais de Doenças , Técnicas Eletrofisiológicas Cardíacas , Junções Comunicantes/metabolismo , Sistema de Condução Cardíaco/metabolismo , Sistema de Condução Cardíaco/fisiopatologia , Perfusão , Coelhos , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/metabolismo , Fibrilação Ventricular/fisiopatologia , Imagens com Corantes Sensíveis à VoltagemRESUMO
We tested a hypothesis that an enhancement of I(Ks) may play a pivotal role in ventricular proarrhythmia under high sympathetic activity. A 2-dimensional ventricular muscle layer was prepared in rabbit hearts, and action potential signals were analyzed by optical mapping. During constant stimulation, isoproterenol (ISP, 0.1 µM) significantly shortened action potential duration (APD); chromanol 293B (30 µM), a selective I(Ks)-blocker, reversed the APD shortening. VTs induced in the presence of ISP lasted longer than in the control, and this was reversed by 293B. E-4031 (0.1 µM), a selective I(Kr)-blocker, did not cause such reversal. Spiral-wave (SW) reentry with ISP was characterized by more stable rotation around a shorter functional block line (FBL) than in the control. After application of 293B, SW reentry was destabilized, and rotation around a longer FBL with prominent drift reappeared. The APD abbreviation by ISP close to the rotation center was more pronounced than in the periphery, leading to an opposite APD gradient (center < periphery) compared with controls. This effect was also reversed by 293B. In conclusion, ß-adrenergic stimulation stabilizes SW reentry most likely though an enhancement of I(Ks). Blockade of I(Ks) may be a promising therapeutic modality in prevention of ventricular tachyarrhythmias under high sympathetic activity.
Assuntos
Adrenérgicos/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio/metabolismo , Sistema Nervoso Simpático/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/prevenção & controle , Cromanos/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Isoproterenol/farmacologia , Miocárdio/metabolismo , Piperidinas/farmacologia , Piridinas/farmacologia , Coelhos , Sulfonamidas/farmacologia , Sistema Nervoso Simpático/metabolismoRESUMO
Bepridil is effective for conversion of atrial fibrillation to sinus rhythm and in the treatment of drug-refractory ventricular tachyarrhythmias. We investigated the effects of bepridil on electrophysiological properties and spiral-wave (SW) reentry in a 2-dimensional ventricular muscle layer of isolated rabbit hearts by optical mapping. Ventricular tachycardia (VT) induced in the presence of bepridil (1 µM) terminated earlier than in the control. Bepridil increased action potential duration (APD) by 5% - 8% under constant pacing and significantly increased the space constant. There was a linear relationship between the wavefront curvature (κ) and local conduction velocity: LCV = LCV0 - D·κ (D, diffusion coefficient; LCV0, LCV at κ = 0). Bepridil significantly increased D and LCV0. The regression lines with and without bepridil crossed at κ = 20 - 40 cm⻹, resulting in a paradoxical decrease of LCV at κ > 40 cm⻹. Dye transfer assay in cultured rat cardiomyocytes confirmed that bepridil increased intercellular coupling. SW reentry in the presence of bepridil was characterized by decremental conduction near the rotation center, prominent drift, and self-termination by collision with boundaries. These results indicate that bepridil causes an increase of intercellular coupling and a moderate APD prolongation, and this combination compromises wavefront propagation near the rotation center of SW reentry, leading to its drift and early termination.
Assuntos
Antiarrítmicos/farmacologia , Bepridil/farmacologia , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Coração/fisiologia , Potenciais de Ação/efeitos dos fármacos , Animais , Bepridil/uso terapêutico , Células Cultivadas , Sistema de Condução Cardíaco/fisiologia , Técnicas In Vitro , Miócitos Cardíacos/fisiologia , Coelhos , Ratos , Estimulação Química , Taquicardia Ventricular/tratamento farmacológico , Taquicardia Ventricular/fisiopatologiaRESUMO
AIMS: Enhanced sympathetic activity during acute ischaemia is arrhythmogenic, but the underlying mechanism is unknown. During ischaemia, a diastolic current flows from the ischaemic to the non-ischaemic myocardium. This 'injury' current can cause ventricular premature beats (VPBs) originating in the non-ischaemic myocardium, especially during a deeply negative T wave in the ischaemic zone. We reasoned that shortening of repolarization in myocardium adjacent to ischaemic myocardium increases the 'injury' current and causes earlier deeply negative T waves in the ischaemic zone, and re-excitation of the normal myocardium. We tested this hypothesis by activation and repolarization mapping during stimulation of the left stellate ganglion (LSG) during left anterior descending coronary artery (LAD) occlusion. METHODS AND RESULTS: In nine pigs, five subsequent episodes of acute ischaemia, separated by 20 min of reperfusion, were produced by occlusion of the LAD and 121 epicardial local unipolar electrograms were recorded. During the third occlusion, left stellate ganglion stimulation (LSGS) was initiated after 3 min for a 30-s period, causing a shortening of repolarization in the normal myocardium by about 100 ms. This resulted in more negative T waves in the ischaemic zone and more VPBs than during the second, control, occlusion. Following the decentralization of the LSG (including removal of the right stellate ganglion and bilateral cervical vagotomy), fewer VPBs occurred during ischaemia without LSGS. During LSGS, the number of VPBs was similar to that recorded before decentralization. CONCLUSION: LSGS, by virtue of shortening of repolarization in the non-ischaemic myocardium by about 100 ms, causes deeply negative T waves in the ischaemic tissue and VPBs originating from the normal tissue adjacent to the ischaemic border.
Assuntos
Potenciais de Ação , Frequência Cardíaca , Coração/inervação , Isquemia Miocárdica/complicações , Gânglio Estrelado/fisiopatologia , Complexos Ventriculares Prematuros/etiologia , Animais , Modelos Animais de Doenças , Estimulação Elétrica , Feminino , Isquemia Miocárdica/fisiopatologia , Sus scrofa , Fatores de Tempo , Complexos Ventriculares Prematuros/fisiopatologiaRESUMO
BACKGROUND: In Japan, intravenous nifekalant (NIF) was often used for direct current cardioversion-resistant ventricular fibrillation (VF), until the use of intravenous amiodarone (AMD) was approved in 2007. The defibrillatory efficacy of NIF and AMD has thus far not been compared for resuscitation. METHODS AND RESULTS: Between August 2007 and April 2009, 403 consecutive out-of-hospital patients with cardiopulmonary arrest were transferred to the Emergency Medical Service of Tokai University. Of these, 30 patients with first defibrillation failure or VF recurrence were enrolled for this NIF/AMD study. The final defibrillation success (and hospital survival rate) was 67% (10/15) in the AMD and 47% (7/15) in the NIF group. The discharge survival rate was 53% (8/15) in the AMD and 21% (4/15) in the NIF group (P = 0.06). Notably, all 4 survivors in the NIF group could take up normal daily life again, whereas this was restricted to only 2 patients from the 11 survivors in the AMD group. The difference is probably partly attributable to longer time from AMD administration to defibrillation success compared with NIF. In the cases of defibrillation failure, VF continued in 4/8 by NIF, however, asystole or pulseless electrical activity occurred in 4/5 patients by AMD. CONCLUSIONS: AMD may be borderline superior over NIF to facilitate defibrillation in out-of-hospital patients with cardiopulmonary arrest. However, from the view point of preservation of brain function, NIF is not inferior to AMD for CPR.
Assuntos
Amiodarona/uso terapêutico , Cardioversão Elétrica , Serviço Hospitalar de Emergência , Parada Cardíaca/tratamento farmacológico , Pirimidinonas/uso terapêutico , Fibrilação Ventricular/tratamento farmacológico , Idoso , Amiodarona/administração & dosagem , Amiodarona/efeitos adversos , Antiarrítmicos/administração & dosagem , Antiarrítmicos/efeitos adversos , Antiarrítmicos/uso terapêutico , Quimioterapia Combinada , Feminino , Parada Cardíaca/etiologia , Parada Cardíaca/terapia , Cardiopatias/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Pirimidinonas/administração & dosagem , Pirimidinonas/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/terapiaRESUMO
BACKGROUND: Dispersion in ventricular repolarization is relevant for arrhythmogenesis. OBJECTIVE: The purpose of this study was to determine the spatiotemporal effects of sympathetic stimulation on ventricular repolarization. METHODS: In 5 anesthetized female open-chest pigs, ventricular repolarization was measured from the anterior, lateral, and posterior walls of the left ventricle (LV) and right ventricle using up to 40 transmural plunge needles (4 electrodes each) before and after left stellate ganglion stimulation (LSGS) and right stellate ganglion stimulation. In addition, LSGS was performed in 3 pigs (2 male, 1 female) before and after verapamil (5-10 mg/h) administration. RESULTS: LSGS yielded a biphasic response in repolarization in the lateral and posterior walls of the LV, with prolongation at â¼5 seconds (10 ± 1.5 ms) and shortening at 20-30 seconds of stimulation (-28.9 ± 4.4 ms) during a monotonic pressure increase. While the initial prolongation was abolished by verapamil, late shortening was augmented. Sequential transections of the vagal nerve and stellate ganglia augmented repolarization dispersion responses to LSGS in 2 of 5 hearts. An equal pressure increase by aortic occlusion resulted in a homogeneous shortening of repolarization in the LV, and the effects were smaller than those during LSGS. Right stellate stimulation shortened repolarization mainly in the anterior LV wall, but the effects were smaller than those of LSGS. CONCLUSION: LSGS first prolongs (through the L-type calcium current) and then shortens repolarization. The effect of LSGS was prominent in the posterior and lateral, not the anterior, LV walls.
Assuntos
Estimulação Elétrica/métodos , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca/fisiologia , Ventrículos do Coração/fisiopatologia , Gânglio Estrelado/fisiopatologia , Taquicardia Ventricular/terapia , Função Ventricular Esquerda/fisiologia , Animais , Modelos Animais de Doenças , Feminino , Masculino , Prognóstico , Suínos , Taquicardia Ventricular/fisiopatologiaRESUMO
Local unipolar electrograms (UEGs) permit assessment of local activation and repolarization times at multiple sites simultaneously. However, UEG-based indexes of local repolarization are still debated, in particular for positive T waves. Previous experimental and computer modeling studies have not been able to terminate the debate. In this study we validate a simple theoretical model of the UEG and use it to explain how repolarization statistics in the UEG relate to those in the action potential. The model reconstructs the UEG by taking the difference between an inverted local action potential and a position-independent remote signal. In normal tissue, this extremely simple model predicts T-wave morphology with surprising accuracy while explaining in a readily understandable way why the instant of repolarization is always related to the steepest upstroke of the UEG, both in positive and negative T waves, and why positive T waves are related to early repolarizing sites, whereas negative T waves are related to late repolarizing sites.
Assuntos
Potenciais de Ação/fisiologia , Eletrocardiografia , Coração/fisiologia , Informática Médica , Modelos Cardiovasculares , Coração/anatomia & histologia , Humanos , Valor Preditivo dos TestesRESUMO
AIM: To investigate ventricular conduction and refractoriness before and after application of rotigaptide, an enhancer of gap junctional conductance, to explanted hearts of patients with heart failure (HF). METHODS AND RESULTS: In six explanted perfused hearts of patients with end-stage HF, activation/repolarization mapping was performed and refractory periods (RPs) and activation recovery intervals (ARIs) were measured before and after application of 50 nM rotigaptide. Rotigaptide caused a decrease of RP from 476 +/- 36 to 453 +/- 31 ms (P < 0.05), but did not change ARI-dispersion. During premature activation along the fibers rotigaptide decreased the minimal activation time (AT(min)) and maximal activation time (AT(max)) significantly from 35 +/- 12 to 24 +/- 9 and from 97 +/- 38 to 43 +/- 7 ms, respectively. Rotigaptide did not change AT(min) and AT(max) during activation perpendicular to the fiber direction. After application of rotigaptide conduction curves normalized in five/six recordings when activation was parallel, but destabilized in three/six hearts when activation was perpendicular to fiber direction. The destabilization was associated with local conduction delays rather than with facilitation of conduction. CONCLUSION: Rotigaptide applied to hearts of patients with end-stage HF shortened RPs normalized conduction curves and increased conduction parallel to fiber direction. However, in 50% of the hearts local slowing of conduction with destabilization of conduction (curves) occurs at sites close to the stimulation site, when activation is perpendicular to fiber direction.
Assuntos
Junções Comunicantes/metabolismo , Sistema de Condução Cardíaco/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Adulto , Eletrofisiologia , Feminino , Junções Comunicantes/efeitos dos fármacos , Sistema de Condução Cardíaco/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/fisiologia , Condução Nervosa/efeitos dos fármacos , Condução Nervosa/fisiologia , Oligopeptídeos/farmacologiaRESUMO
The electrocardiogram (ECG) reveals that heart chamber activation and repolarization are much faster in mammals and birds compared to ectothermic vertebrates of similar size. Temperature, however, affects electrophysiology of the heart and most data from ectotherms are determined at body temperatures lower than those of mammals and birds. The present manuscript is a review of the effects of temperature on intervals in the ECG of ectothermic and endothermic vertebrates rather than a hypothesis-testing original research article. However, the conclusions are supported by the inclusion of original data (Iguana iguana, Nâ¯=â¯4; Python regius, Nâ¯=â¯5; Alligator mississippiensis, Nâ¯=â¯4). Most comparisons were of animals of approximately 1â¯kg. Compared to mammals and birds, the reptiles at 35-37⯰C had 4 fold lower heart rates, 2 fold slower atrial and ventricular conduction (longer P- and QRS-wave durations), and 4 fold longer PR intervals (atrioventricular delay) and QT intervals (total ventricular repolarization). We conclude that the faster chamber activation in endotherms cannot be explained by temperature alone. Based on histology, we show that endotherms have a more compact myocardial architecture. In mammals, disorganization of the compact wall by fibrosis associates with conduction slowing and we suggest the compact tissue architecture allows for faster chamber activation. The short cardiac cycle that characterizes mammals and birds, however, is predominantly accommodated by shortening of the atrioventricular delay and the QT interval, which is so long in a 1â¯kg iguana that it compares to that of an elephant.
Assuntos
Evolução Biológica , Regulação da Temperatura Corporal , Eletrocardiografia , Vertebrados/fisiologia , Animais , Coração/fisiologia , HumanosRESUMO
T-type Ca2+ channels (TCCs) are involved in cardiac cell growth and proliferation in cultured cardiomyocytes. Underlying molecular mechanisms are not well understood. In this study, we investigated the role of TCCs in signal transduction in cardiac hypertrophy compared with L-type Ca2+ channels (LCCs). Cardiomyocytes dissociated from neonatal mouse ventricles were cultured until stabilization. Cell hypertrophy was induced by reapplication of 1% fatal bovine serum (FBS) following a period (24 h) of FBS depletion. Cell surface area increased from 862+/-73 microm2 to 2153+/-131 microm2 by FBS stimulation in control (250+/-1.8%). T-type Ca2+ current (I(CaT)) was inhibited dose-dependently by kurtoxin (KT) and efonidipine (ED) with IC50 0.07 microM and 3.2 microM, respectively in whole-cell voltage clamp. On the other hand, 1 microM KT which inhibits I(CaT) over 90% did not effect on L-type Ca2+ current (I(CaL)). 10 microM ED had the ability of I(CaL) blockade as well as that of I(CaT) blockade. 3 microM nisoldipine (ND) suppressed I(CaL) by over 80%. The increase in cell surface area following reapplication of FBS as observed in control (250+/-1.8%) was significantly reduced in the presence of 1 microM KT (216+/-1.2%) and virtually abolished in the presence of 10 microM ED (97+/-0.8%) and 3 microM ND (80+/-1.1%). Hypertrophy was associated with an increase in BNP mRNA of 316+/-3.6% in control and this increase was reduced as well in the presence of 1 microM KT (254+/-1.8%) and almost abolished in the presence of 10 microM ED (116+/-1.1%) and 3 muM ND (93+/-0.8%). Immunolabeling showed that translocation of nuclear factor of activated T cells (NFAT3) into the nucleus in response to FBS stimulation was markedly inhibited by either KT or ED as well as ND. Calcineurin phosphatase activity was upregulated 2.2-fold by FBS, but KT, ED and ND decreased this upregulation (1.7-fold, 0.8-fold, and 0.7-fold with KT, ED and ND respectively). These results suggest that blockade of Ca2+ entry into cardiomyocytes via TCCs may block pathophysiological signaling pathways leading to hypertrophy as well as via LCCs. The mechanism may be the inhibition of calcineurin-mediated NFAT3 activation resulting in prevention of its translocation into the nucleus.
Assuntos
Calcineurina/metabolismo , Bloqueadores dos Canais de Cálcio/metabolismo , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo T/metabolismo , Hipertrofia , Miocárdio , Miócitos Cardíacos/metabolismo , Fatores de Transcrição NFATC/metabolismo , Transporte Ativo do Núcleo Celular/fisiologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Bovinos , Células Cultivadas , Di-Hidropiridinas/metabolismo , Camundongos , Miocárdio/citologia , Miocárdio/patologia , Miócitos Cardíacos/citologia , Peptídeo Natriurético Encefálico/genética , Peptídeo Natriurético Encefálico/metabolismo , Neurotoxinas/metabolismo , Nisoldipino/metabolismo , Nitrofenóis/metabolismo , Compostos Organofosforados/metabolismo , Técnicas de Patch-Clamp , Venenos de Escorpião/metabolismoRESUMO
Increased consumption of fish rich in omega-3 polyunsaturated fatty acids (omega3-PUFAs) is associated with decreased incidence of sudden cardiac death in post-myocardial infarction patients, but is also related to increased incidence of sudden death and arrhythmias in patients with acute myocardial ischemia. This review discusses the possible pro- and antiarrhythmic mechanisms of omega3-PUFAs in relation to various cardiac pathologies. Differences between circulating and incorporated omega3-PUFAs with respect to electrophysiology are emphasized. We conclude that omega3-PUFAs alter cardiac electrophysiology and thereby may be pro- or antiarrhythmic, dependent on the mechanism of arrhythmia. As omega3-PUFAs may be antiarrhythmic under conditions that favour triggered activity, they may facilitate re-entrant arrhythmias. This may explain the contradictory outcomes of increased intake of fish oil on sudden death and arrhythmias in clinical trials. Advice to increase intake of omega3-PUFA supplements or fatty fish should be tailored to individual patients with respect to the arrhythmogenic mechanisms associated with the underlying pathology.
Assuntos
Arritmias Cardíacas/etiologia , Arritmias Cardíacas/prevenção & controle , Dieta , Óleos de Peixe , Potenciais de Ação/fisiologia , Animais , Suplementos Nutricionais , Eletrocardiografia , Humanos , Canais Iônicos/metabolismoRESUMO
OBJECTIVE: The contribution of regional electrophysiologic heterogeneity to the T-wave changes of long-term cardiac memory (CM) is not known. We mapped activation and repolarization in dogs after induction of CM and in sham animals. METHODS AND RESULTS: CM was induced by three weeks of AV-sequential pacing at the anterior free wall of the left ventricle (LV), midway between apex and base in 5 dogs. In 4 sham controls a pacemaker was implanted but ventricular pacing was not performed. At 3 weeks, unipolar electrograms were recorded (98 epicardial, 120 intramural and endocardial electrodes) during atrial stimulation (cycle length 450 ms). Activation times (AT) and repolarization times (RT) were measured and activation recovery intervals (ARIs) calculated. CM was associated with 1) deeper T waves on ECG, with no change in QT interval; 2) longer activation time at the site of stimulation in CM (29.7+/-1.0, X+/-SEM) than sham (23.9+/-1.3 ms p<0.01); 3) an LV transmural gradient in repolarization time such that repolarization at the epicardium terminated 12.4+/-2.4 ms later than at the endocardium p<0.01), in contrast to no gradient in shams (2.7+/-4.2 ms); in memory dogs, the repolarization time gradient was greatest at sites around the pacing electrode varying from 13.1+/-2.3 ms to 25.5+/-3.8 ms; 4) more negative left ventricular potentials at the peak of the body surface T wave (-4.9+/-0.8 vs -2.2+/-0.4 mV; p<0.05) but no altered right ventricular epicardial T-wave potentials. ARIs did not differ between groups. Right ventricular activation was delayed but was not associated with altered repolarization because of compensatory shortening of the right ventricular ARIs. CONCLUSION: CM-induced T-wave changes are caused by evolution of transmural repolarization gradients manifested during atrial stimulation that are maximal near the site of ventricular pacing.
Assuntos
Estimulação Cardíaca Artificial , Eletrocardiografia , Sistema de Condução Cardíaco/fisiologia , Potenciais de Ação , Animais , Cães , Endocárdio/fisiologia , Masculino , Pericárdio/fisiologia , Fatores de Tempo , Função VentricularRESUMO
OBJECTIVE: Dietary supplementation with fish oil-derived n-3 fatty acids reduces mortality in patients with myocardial infarction, but may have adverse effects in angina patients. The underlying electrophysiologic mechanisms are poorly understood. We studied the arrhythmias and the electrophysiologic changes during regional ischemia in hearts from pigs fed a diet rich in fish oil. METHODS: Pigs received diets rich in fish oil, in sunflower oil, or a control diet for 8 weeks. Hearts were isolated and perfused. Ischemia was created by occluding the left anterior descending artery. Diastolic stimulation threshold, refractory period, conduction velocity, activation recovery intervals and the maximum downstroke velocity of 176 electrograms were measured in the ischemic zone. Spontaneous arrhythmias during 75 min of regional ischemia were counted. RESULTS: More episodes of spontaneous ischemia-induced sustained ventricular tachycardia and ventricular fibrillation occurred in the fish oil and sunflower oil group than in the control group. More inexcitable myocardium was present in the ischemic zone in the group fed fish oil or sunflower oil than in the control group after 20 min of ischemia. After 40 min of ischemia, more block occurred in the control group than in the other groups. The downstroke velocity of the electrograms in the ischemic border zone was lower in the fish oil group and sunflower oil group than in the control after 20 min. CONCLUSIONS: A diet rich in fish oil results in proarrhythmia compared to a control diet during regional ischemia in pigs. Myocardial excitability is reduced in the fish oil and sunflower oil group during the early phase of arrhythmogenesis. In the late phase of arrhythmogenesis, excitability is more reduced in the control group than in the fish oil and sunflower oil group.
Assuntos
Arritmias Cardíacas/induzido quimicamente , Ácidos Graxos Ômega-3/administração & dosagem , Animais , Arritmias Cardíacas/fisiopatologia , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/análise , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/análise , Ácido Eicosapentaenoico/sangue , Eletrocardiografia , Coração/fisiopatologia , Masculino , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Perfusão , Óleos de Plantas/administração & dosagem , Óleo de Girassol , SuínosRESUMO
BACKGROUND: Patients with heart failure (HF) have an increased QRS duration, usually attributed to decreased conduction velocity (CV) due to ionic remodeling but which may alternatively result from increased heart size or cellular uncoupling. We investigated the relationship between QRS width, heart size, intercellular coupling, and CV in a rabbit model of moderate HF and in computer simulations. METHODS AND RESULTS: HF was induced by pressure-volume overload. Heart weight (21.1+/-0.5 versus 10.2+/-0.4 g, mean+/-SEM; P<0.01) and QRS duration (58+/-1 versus 50+/-1 ms; P<0.01) were increased in HF versus control. Longitudinal CV (thetaL; 79+/-2 versus 67+/-4 cm/s; P<0.01) and transversal subepicardial CV (thetaT; 43+/-2 versus 37+/-2 cm/s; P<0.05) were higher in HF than in controls. Transmural CV (thetaTM) was unchanged (25+/-2 versus 24+/-1 cm/s; P=NS). Patch-clamp experiments demonstrated that sodium current was unchanged in HF versus control. Immunohistochemical experiments revealed that connexin43 content was reduced in midmyocardium but unchanged in subepicardium. Myocyte dimensions were increased in HF by approximately 30%. Simulated strands of mammalian ventricular cells (Luo-Rudy dynamic model) revealed increased thetaL and thetaT with increased myocyte size; however, increased CV could not compensate for increased strand size of longitudinally coupled cells, and consequently, total activation time was longer. CONCLUSIONS: Increased myocyte size combined with the observed expression pattern of connexin43 yields increased thetaL and thetaT and unchanged thetaTM in our nonischemic model of HF. A hypertrophied left ventricle together with insufficiently increased thetaL and unaltered thetaTM results in a prolonged QRS duration.
Assuntos
Cardiomegalia/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Insuficiência Cardíaca/patologia , Animais , Cardiomegalia/patologia , Comunicação Celular , Tamanho Celular , Simulação por Computador , Conexina 43/análise , Eletrocardiografia , Sistema de Condução Cardíaco/patologia , Insuficiência Cardíaca/fisiopatologia , Hipertrofia Ventricular Esquerda , Técnicas In Vitro , Células Musculares/patologia , CoelhosRESUMO
Most textbook knowledge on ventricular repolarization is based on animal data rather than on data from the in vivo human heart. Yet, these data have been extrapolated to the human heart, often without an appropriate caveat. Here, we review multiple aspects of repolarization, from basic membrane currents to cellular aspects including extrinsic factors such as the effects of the sympathetic nervous system. We critically discuss some mechanistic aspects of the genesis of the T-wave of the ECG in the human heart. Obviously, the T-wave results from the summation of repolarization all over the heart. The T-wave in a local electrogram ideally reflects local repolarization. The repolarization moment is composed of the moment of local activation plus local action potential duration (APD) at 90% repolarization (APD90). The duration of the latter largely depends on the balance between L-type Ca2+ current and the delayed rectifier currents. Generally speaking, there is an inverse relationship between local activation time and local APD90, leading to less dispersion in repolarization moments than in activation moments or in APD90. In transmural direction, the time needed for activation from endocardium toward epicardium has been considered to be overcompensated by shorter APD90 at the epicardium, leading to the earliest repolarization at the subepicardium. In addition, mid-myocardial cells would display the latest repolarization moments. The sparse human data available, however, do not show any transmural dispersion in repolarization moment. Also, the effect of adrenergic stimulation on APD90 has been studied mainly in animals. Again, sparse human data suggest that the effect of adrenergic stimulation is different in the human heart compared to many other mammalian hearts. Finally, aspects of the long QT syndrome are discussed, because this intrinsic genetic disease results from repolarization disorders with extrinsic aspects.
Assuntos
Eletrocardiografia , Eletrofisiologia , Sistema de Condução Cardíaco/fisiologia , Coração/fisiologia , Sistema Nervoso Simpático/fisiologia , Função Ventricular , Potenciais de Ação/fisiologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Canais de Cálcio Tipo L/fisiologia , Humanos , Síndrome do QT Longo/genética , Síndrome do QT Longo/patologia , Miocárdio/citologia , Miocárdio/metabolismoRESUMO
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.
Assuntos
Eletrocardiografia , Sistema de Condução Cardíaco/fisiologia , Potenciais de Ação , Análise de Variância , Animais , Estimulação Cardíaca Artificial , Cães , Eletrodos Implantados , Técnicas Eletrofisiológicas Cardíacas , Endocárdio/fisiologia , Feminino , Processamento de Imagem Assistida por Computador , Modelos Lineares , Masculino , Modelos Animais , Modelos Cardiovasculares , Pericárdio/fisiologia , Projetos de Pesquisa , Função VentricularRESUMO
BACKGROUND: Fish oil reduces the incidence of sudden cardiac death in postmyocardial infarction patients. Triggered activity is the principal mechanism of arrhythmogenesis under these conditions. OBJECTIVE: The purpose of this study was to test whether dietary fish oil in pigs inhibits Ca2+ overload-induced triggered activity. METHODS: Pigs were fed a diet of fish oil or sunflower oil for 8 weeks. Ventricular myocytes (omega3: fish oil, n = 11; control: sunflower oil, n = 8) were isolated by enzymatic dissociation and used for patch clamp studies and intracellular Ca2+ recordings. Triggered activity was induced by rapid pacing in the presence of norepinephrine. RESULTS: Dietary fish oil reduced the incidence of triggered action potentials and delayed afterdepolarizations compared to control (9.1% in omega3 and 84.6% in control, P <.05), concomitant with a reduction in spontaneous Ca2+ release. Dietary fish oil prevented Ca2+ overload and reduced action potential prolongation in response to norepinephrine (DeltaAPD(90): 23.2 +/- 8.5 ms in omega3 and 107.4 +/- 15.9 in control, P <.05). omega3 myocytes displayed decreased sarcoplasmic reticulum Ca2+ content, reduced L-type Ca2+ current (I(Ca,L)), and less recruitment of the Na+/Ca2+ exchange current (I(NCX)) in response to norepinephrine compared to control. In the absence of norepinephrine, the slow component of the delayed rectifier current (I(Ks)) was larger in omega3 myocytes. In the presence of norepinephrine, I(Ks) increased to the same level in omega3 and control myocytes. CONCLUSION: Dietary fish oil reduces the incidence of triggered activity and prevents Ca2+ overload and AP prolongation in response to norepinephrine. Fish oil may prevent arrhythmias in patients with heart failure.