RESUMO
Mesenchymal stem cells (MSCs) have been shown to improve cardiac electrophysiology when administered in the setting of acute myocardial infarction. However, the electrophysiological phenotype of MSCs in situ is not clear. We hypothesize that MSCs delivered intramyocardially to cryoinjured myocardium can engraft, but will not actively generate, action potentials. Cryoinjury-induced scar was created on the left ventricular epicardial surface of adult rat hearts. Within 30 min, hearts were injected with saline (sham, n = 11) or bone marrow-derived MSCs (2 × 10(6)) labeled with 1,1'-dioctadecyl-3,3,3,3'-tetramethylindocarbocyanine percholate (DiI; n = 16). At 3 wk, optical mapping and cell isolation were used to measure optical action potentials and calcium transients, respectively. Histological analysis confirmed subepicardial scar thickness and the presence of DiI-positive cells that express connexin-43. Optical action potential amplitude within the scar at MSC-positive sites (53.8 ± 14.3%) was larger compared with sites devoid of MSCs (35.3 ± 14.2%, P < 0.05) and sites within the scar of shams (33.5 ± 6.9%, P < 0.05). Evidence of simultaneous action potential upstroke, the loss of action potential activity following ablation of adjacent viable myocardium, and no rapid calcium transient response in isolated DiI+ cells suggest that the electrophysiological influence of engrafted MSCs is electrotonic. MSCs can engraft when directly injected into a cryoinjury and are associated with evidence of action potential activity. However, our results suggest that this activity is not due to generation of action potentials, but rather passive influence coupled from neighboring viable myocardium.
Assuntos
Sistema de Condução Cardíaco/fisiopatologia , Ventrículos do Coração/fisiopatologia , Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio/cirurgia , Miocárdio/patologia , Imagens com Corantes Sensíveis à Voltagem , Potenciais de Ação , Animais , Sinalização do Cálcio , Carbocianinas , Comunicação Celular , Conexina 43/metabolismo , Criocirurgia , Modelos Animais de Doenças , Corantes Fluorescentes , Sistema de Condução Cardíaco/metabolismo , Sistema de Condução Cardíaco/patologia , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Masculino , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Ratos , Ratos Endogâmicos Lew , Regeneração , Fatores de TempoRESUMO
BACKGROUND: Idiopathic left ventricular arrhythmias (VAs) and those caused by structural heart disease can originate from the papillary muscles, fascicles, and mitral annulus. Differentiation of these arrhythmias can be challenging because they present with a right bundle branch block morphology by electrocardiography. We sought to identify clinical, electrocardiographic, and electrophysiological features that distinguish these left VAs in patients with and without structural heart disease. METHOD AND RESULTS: Patients undergoing catheter ablation for papillary muscle, fascicular, or mitral annular VAs were studied. Demographic data and electrocardiographic and electrophysiological findings were analyzed. Fifty-two VAs in 51 patients (32 [63%] male; mean age 61±15 years) with papillary muscle (n=18), fascicular (n=15), and mitral annular (n=19) origins were studied. Patients with papillary muscle VAs were older and had higher prevalence of left ventricular dysfunction (67% versus 13% of fascicular VA patients [P=0.009]) and coronary artery disease (78% versus 37% of mitral annular VA patients [P=0.036]). Papillary muscle VAs were distinguished electrocardiographically from fascicular VAs by longer QRS durations and lower prevalence of rAssuntos
Arritmias Cardíacas/diagnóstico
, Eletrocardiografia
, Técnicas Eletrofisiológicas Cardíacas
, Ventrículos do Coração/fisiopatologia
, Valva Mitral/fisiopatologia
, Músculos Papilares/fisiopatologia
, Potenciais de Ação
, Adulto
, Idoso
, Idoso de 80 Anos ou mais
, Algoritmos
, Arritmias Cardíacas/epidemiologia
, Arritmias Cardíacas/fisiopatologia
, Arritmias Cardíacas/cirurgia
, Ablação por Cateter
, Doença da Artéria Coronariana/diagnóstico
, Doença da Artéria Coronariana/epidemiologia
, Diagnóstico Diferencial
, Feminino
, Frequência Cardíaca
, Ventrículos do Coração/cirurgia
, Humanos
, Imageamento por Ressonância Magnética
, Masculino
, Pessoa de Meia-Idade
, Valva Mitral/cirurgia
, Músculos Papilares/cirurgia
, Valor Preditivo dos Testes
, Prevalência
, Recidiva
, Estudos Retrospectivos
, Fatores de Risco
, Processamento de Sinais Assistido por Computador
, Fatores de Tempo
, Disfunção Ventricular Esquerda/diagnóstico
, Disfunção Ventricular Esquerda/epidemiologia
, Disfunção Ventricular Esquerda/fisiopatologia
, Função Ventricular Esquerda
RESUMO
OPINION STATEMENT: Catheter ablation has emerged as an important therapy for atrial fibrillation. The past decade has seen tremendous growth in the use of this technology, as well as the use of novel sources and methods of energy delivery. As the volume and complexity of catheter ablation procedures for atrial fibrillation have increased, our understanding of the range of procedural complications has also grown. Thromboembolic events, esophageal injury, and phrenic nerve palsy represent some of the potential complications of atrial fibrillation ablation that remain challenging to prevent and manage. In this review, we discuss the strategies for the diagnosis, prevention, and treatment of complications from catheter ablation of atrial fibrillation. Rapid recognition and treatment of these complications are critical for the improvement of patient outcomes.
RESUMO
INTRODUCTION: Mesenchymal stem cells (MSCs) have been associated with reduced arrhythmias; however, the mechanism of this action is unknown. In addition, limited retention and survival of MSCs can significantly reduce efficacy. We hypothesized that MSCs can improve impulse conduction and that alginate hydrogel will enhance retention of MSCs in a model of healed myocardial infarction (MI). METHODS AND RESULTS: Four weeks after temporary occlusion of the left anterior descending artery (LAD), pigs (n = 13) underwent a sternotomy to access the infarct and then were divided into two studies. In study 1, designed to investigate impulse conduction, animals were administered, by border zone injection, 9-15 million MSCs (n = 7) or phosphate-buffered saline (PBS) (control MI, n = 5). Electrogram width measured in the border zone 2 weeks after injections was significantly decreased with MSCs (-30 ± 8 ms, p < 0.008) but not in shams (4 ± 10 ms, p = NS). Optical mapping from border zone tissue demonstrated that conduction velocity was higher in regions with MSCs (0.49 ± 0.03 m/s) compared to regions without MSCs (0.39 ± 0.03 m/s, p < 0.03). In study 2, designed to investigate MSC retention, animals were administered an equal number of MSCs suspended in either alginate (2 or 1 % w/v) or PBS (n = 6/group) by border zone injection. Greater MSC retention and survival were observed with 2% alginate compared to PBS or 1% alginate. Confocal immunofluorescence demonstrated that MSCs survive and are associated with expression of connexin-43 (Cx43) for either PBS (control), 1%, or 2% alginate. CONCLUSIONS: For the first time, we are able to directly associate MSCs with improved impulse conduction and increased retention and survival using an alginate scaffold in a clinically relevant model of healed MI.