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[PMID]:28747397
[Au] Autor:Gao H; Aderhold A; Mangion K; Luo X; Husmeier D; Berry C
[Ad] Endereço:School of Mathematics and Statistics, University of Glasgow, Glasgow, UK hao.gao@glasgow.ac.uk.
[Ti] Título:Changes and classification in myocardial contractile function in the left ventricle following acute myocardial infarction.
[So] Source:J R Soc Interface;14(132), 2017 Jul.
[Is] ISSN:1742-5662
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In this research, we hypothesized that novel biomechanical parameters are discriminative in patients following acute ST-segment elevation myocardial infarction (STEMI). To identify these biomechanical biomarkers and bring computational biomechanics 'closer to the clinic', we applied state-of-the-art multiphysics cardiac modelling combined with advanced machine learning and multivariate statistical inference to a clinical database of myocardial infarction. We obtained data from 11 STEMI patients (ClinicalTrials.gov NCT01717573) and 27 healthy volunteers, and developed personalized mathematical models for the left ventricle (LV) using an immersed boundary method. Subject-specific constitutive parameters were achieved by matching to clinical measurements. We have shown, for the first time, that compared with healthy controls, patients with STEMI exhibited increased LV wall active tension when normalized by systolic blood pressure, which suggests an increased demand on the contractile reserve of remote functional myocardium. The statistical analysis reveals that the required patient-specific contractility, normalized active tension and the systolic myofilament kinematics have the strongest explanatory power for identifying the myocardial function changes post-MI. We further observed a strong correlation between two biomarkers and the changes in LV ejection fraction at six months from baseline (the required contractility ( = - 0.79, < 0.01) and the systolic myofilament kinematics ( = 0.70, = 0.02)). The clinical and prognostic significance of these biomechanical parameters merits further scrutinization.
[Mh] Termos MeSH primário: Ventrículos do Coração/fisiopatologia
Contração Miocárdica/fisiologia
Infarto do Miocárdio/fisiopatologia
Função Ventricular
[Mh] Termos MeSH secundário: Adulto
Idoso
Estudos de Casos e Controles
Feminino
Ventrículos do Coração/patologia
Seres Humanos
Masculino
Meia-Idade
Infarto do Miocárdio/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE


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[PMID]:28460776
[Au] Autor:Di Lullo L; Bellasi A; Barbera V; Russo D; Russo L; Di Iorio B; Cozzolino M; Ronco C
[Ad] Endereço:Department of Nephrology and Dialysis, L. Parodi - Delfino Hospital, Colleferro Rome, Italy. Electronic address: dilulloluca69@gmail.com.
[Ti] Título:Pathophysiology of the cardio-renal syndromes types 1-5: An uptodate.
[So] Source:Indian Heart J;69(2):255-265, 2017 Mar - Apr.
[Is] ISSN:0019-4832
[Cp] País de publicação:India
[La] Idioma:eng
[Ab] Resumo:According to the recent definition proposed by the Consensus conference on Acute Dialysis Quality Initiative Group, the term cardio-renal syndrome (CRS) has been used to define different clinical conditions in which heart and kidney dysfunction overlap. Type 1 CRS (acute cardio- renal syndrome) is characterized by acute worsening of cardiac function leading to AKI (5, 6) in the setting of active cardiac disease such as ADHF, while type - 2 CRS occurs in a setting of chronic heart disease. Type 3 CRS is closely link to acute kidney injury (AKI), while type 4 represent cardiovascular involvement in chronic kidney disese (CKD) patients. Type 5 CRS represent cardiac and renal involvement in several diseases such as sepsis, hepato - renal syndrome and immune - mediated diseases.
[Mh] Termos MeSH primário: Síndrome Cardiorrenal/fisiopatologia
Função Ventricular/fisiologia
[Mh] Termos MeSH secundário: Progressão da Doença
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:29342222
[Au] Autor:Amar A; Zlochiver S; Barnea O
[Ad] Endereço:Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel.
[Ti] Título:Mechano-electric feedback effects in a three-dimensional (3D) model of the contracting cardiac ventricle.
[So] Source:PLoS One;13(1):e0191238, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mechano-electric feedback affects the electrophysiological and mechanical function of the heart and the cellular, tissue, and organ properties. To determine the main factors that contribute to this effect, this study investigated the changes in the action potential characteristics of the ventricle during contraction. A model of stretch-activated channels was incorporated into a three-dimensional multiscale model of the contracting ventricle to assess the effect of different preload lengths on the electrophysiological behavior. The model describes the initiation and propagation of the electrical impulse, as well as the passive (stretch) and active (contraction) changes in the cardiac mechanics. Simulations were performed to quantify the relationship between the cellular activation and recovery patterns as well as the action potential durations at different preload lengths in normal and heart failure pathological conditions. The simulation results showed that heart failure significantly affected the excitation propagation parameters compared to normal condition. The results showed that the mechano-electrical feedback effects appear to be most important in failing hearts with low ejection fraction.
[Mh] Termos MeSH primário: Modelos Cardiovasculares
Contração Miocárdica/fisiologia
[Mh] Termos MeSH secundário: Animais
Fenômenos Biomecânicos
Simulação por Computador
Fenômenos Eletrofisiológicos
Retroalimentação Fisiológica
Insuficiência Cardíaca/patologia
Insuficiência Cardíaca/fisiopatologia
Ventrículos do Coração/anatomia & histologia
Seres Humanos
Imagem Tridimensional
Função Ventricular
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191238


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[PMID]:28912187
[Au] Autor:Lee TM; Hsu DT; Kantor P; Towbin JA; Ware SM; Colan SD; Chung WK; Jefferies JL; Rossano JW; Castleberry CD; Addonizio LJ; Lal AK; Lamour JM; Miller EM; Thrush PT; Czachor JD; Razoky H; Hill A; Lipshultz SE
[Ad] Endereço:From the Department of Pediatrics, Columbia University Medical Center, New York, NY (T.M.L., W.K.C., L.J.A.); Department of Pediatrics, Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY (D.T.H., J.M.L.); Department of Pediatrics, Stollery Children's Hospital, Univ
[Ti] Título:Pediatric Cardiomyopathies.
[So] Source:Circ Res;121(7):855-873, 2017 Sep 15.
[Is] ISSN:1524-4571
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pediatric cardiomyopathies are rare diseases with an annual incidence of 1.1 to 1.5 per 100 000. Dilated and hypertrophic cardiomyopathies are the most common; restrictive, noncompaction, and mixed cardiomyopathies occur infrequently; and arrhythmogenic right ventricular cardiomyopathy is rare. Pediatric cardiomyopathies can result from coronary artery abnormalities, tachyarrhythmias, exposure to infection or toxins, or secondary to other underlying disorders. Increasingly, the importance of genetic mutations in the pathogenesis of isolated or syndromic pediatric cardiomyopathies is becoming apparent. Pediatric cardiomyopathies often occur in the absence of comorbidities, such as atherosclerosis, hypertension, renal dysfunction, and diabetes mellitus; as a result, they offer insights into the primary pathogenesis of myocardial dysfunction. Large international registries have characterized the epidemiology, cause, and outcomes of pediatric cardiomyopathies. Although adult and pediatric cardiomyopathies have similar morphological and clinical manifestations, their outcomes differ significantly. Within 2 years of presentation, normalization of function occurs in 20% of children with dilated cardiomyopathy, and 40% die or undergo transplantation. Infants with hypertrophic cardiomyopathy have a 2-year mortality of 30%, whereas death is rare in older children. Sudden death is rare. Molecular evidence indicates that gene expression differs between adult and pediatric cardiomyopathies, suggesting that treatment response may differ as well. Clinical trials to support evidence-based treatments and the development of disease-specific therapies for pediatric cardiomyopathies are in their infancy. This compendium summarizes current knowledge of the genetic and molecular origins, clinical course, and outcomes of the most common phenotypic presentations of pediatric cardiomyopathies and highlights key areas where additional research is required. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02549664 and NCT01912534.
[Mh] Termos MeSH primário: Cardiomiopatias
[Mh] Termos MeSH secundário: Idade de Início
Técnicas de Imagem Cardíaca
Cardiomiopatias/diagnóstico
Cardiomiopatias/epidemiologia
Cardiomiopatias/genética
Cardiomiopatias/terapia
Marcadores Genéticos
Predisposição Genética para Doença
Seres Humanos
Incidência
Técnicas de Diagnóstico Molecular
Mutação
Miocárdio/patologia
Fenótipo
Prognóstico
Fatores de Risco
Função Ventricular
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Genetic Markers)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1161/CIRCRESAHA.116.309386


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[PMID]:28912188
[Au] Autor:Jan MF; Tajik AJ
[Ad] Endereço:From Aurora Cardiovascular Services, Aurora Sinai/Aurora St. Luke's Medical Centers, Milwaukee, WI.
[Ti] Título:Modern Imaging Techniques in Cardiomyopathies.
[So] Source:Circ Res;121(7):874-891, 2017 Sep 15.
[Is] ISSN:1524-4571
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Modern advanced imaging techniques have allowed increasingly more rigorous assessment of the cardiac structure and function of several types of cardiomyopathies. In contemporary cardiology practice, echocardiography and cardiac magnetic resonance imaging are widely used to provide a basic framework in the evaluation and management of cardiomyopathies. Echocardiography is the quintessential imaging technique owing to its unique ability to provide real-time images of the beating heart with good temporal resolution, combined with its noninvasive nature, cost-effectiveness, availability, and portability. Cardiac magnetic resonance imaging provides data that are both complementary and uniquely distinct, thus allowing for insights into the disease process that until recently were not possible. The new catchphrase in the evaluation of cardiomyopathies is multimodality imaging, which is purported to be the efficient integration of various methods of cardiovascular imaging to improve the ability to diagnose, guide therapy, or predict outcomes. It usually involves an integrated approach to the use of echocardiography and cardiac magnetic resonance imaging for the assessment of cardiomyopathies, and, on occasion, single-photon emission computed tomography and such specialized techniques as pyrophosphate scanning.
[Mh] Termos MeSH primário: Técnicas de Imagem Cardíaca
Cardiomiopatias/diagnóstico por imagem
[Mh] Termos MeSH secundário: Fenômenos Biomecânicos
Cardiomiopatias/patologia
Cardiomiopatias/fisiopatologia
Cardiomiopatias/terapia
Ecocardiografia
Seres Humanos
Imagem por Ressonância Magnética
Contração Miocárdica
Miocárdio/patologia
Valor Preditivo dos Testes
Prognóstico
Tomografia Computadorizada de Emissão
Tomografia Computadorizada por Raios X
Função Ventricular
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1161/CIRCRESAHA.117.309600


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[PMID]:28912180
[Au] Autor:McNally EM; Mestroni L
[Ad] Endereço:From the Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago IL (E.M.M.); and Cardiovascular Institute, University of Colorado Anschutz Medical Campus, Aurora (L.M.). elizabeth.mcnally@northwestern.edu Luisa.Mestroni@ucdenver.edu.
[Ti] Título:Dilated Cardiomyopathy: Genetic Determinants and Mechanisms.
[So] Source:Circ Res;121(7):731-748, 2017 Sep 15.
[Is] ISSN:1524-4571
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nonischemic dilated cardiomyopathy (DCM) often has a genetic pathogenesis. Because of the large number of genes and alleles attributed to DCM, comprehensive genetic testing encompasses ever-increasing gene panels. Genetic diagnosis can help predict prognosis, especially with regard to arrhythmia risk for certain subtypes. Moreover, cascade genetic testing in family members can identify those who are at risk or with early stage disease, offering the opportunity for early intervention. This review will address diagnosis and management of DCM, including the role of genetic evaluation. We will also overview distinct genetic pathways linked to DCM and their pathogenetic mechanisms. Historically, cardiac morphology has been used to classify cardiomyopathy subtypes. Determining genetic variants is emerging as an additional adjunct to help further refine subtypes of DCM, especially where arrhythmia risk is increased, and ultimately contribute to clinical management.
[Mh] Termos MeSH primário: Cardiomiopatia Dilatada/genética
Mutação
Miocárdio/patologia
Função Ventricular
[Mh] Termos MeSH secundário: Animais
Biópsia
Técnicas de Imagem Cardíaca
Cardiomiopatia Dilatada/patologia
Cardiomiopatia Dilatada/fisiopatologia
Cardiomiopatia Dilatada/terapia
Análise Mutacional de DNA
Marcadores Genéticos
Predisposição Genética para Doença
Seres Humanos
Técnicas de Diagnóstico Molecular
Fenótipo
Valor Preditivo dos Testes
Prognóstico
Medição de Risco
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Genetic Markers)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1161/CIRCRESAHA.116.309396


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[PMID]:28912182
[Au] Autor:Nishimura RA; Seggewiss H; Schaff HV
[Ad] Endereço:From the Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (R.A.N.); Medizinische Klinik 1, Leopoldina Krankenhaus, Schweinfurt, Germany (H.S.); and Department of Cardiovascular Surgery, Rochester, MN (H.V.S.). rnishimura@mayo.edu.
[Ti] Título:Hypertrophic Obstructive Cardiomyopathy: Surgical Myectomy and Septal Ablation.
[So] Source:Circ Res;121(7):771-783, 2017 09 15.
[Is] ISSN:1524-4571
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hypertrophic cardiomyopathy is a genetic disorder characterized by marked hypertrophy of the myocardium. It is frequently accompanied by dynamic left ventricular outflow tract obstruction and symptoms of dyspnea, angina, and syncope. The initial therapy for symptomatic patients with obstruction is medical therapy with ß-blockers and calcium antagonists. However, there remain a subset of patients who have continued severe symptoms, which are unresponsive to medical therapy. These patients can be treated with septal reduction therapy, either surgical septal myectomy or alcohol septal ablation. When performed by experienced operators working in high-volume centers, septal myectomy is highly effective with a >90% relief of obstruction and improvement in symptoms. The perioperative mortality rate for isolated septal myectomy in most centers is <1%. Alcohol septal ablation is a less invasive treatment. In many patients, the hemodynamic and clinical results are comparable to that of septal myectomy. However, the results of alcohol septal ablation are dependent on the septal perforator artery supplying the area of the contact between the hypertrophied septum and the anterior leaflet of the mitral valve. There are some patients, particularly younger patients with severe hypertrophy, who do not uniformly experience complete relief of obstruction and symptoms. Both techniques of septal reduction therapy are highly operator dependent. The final decision as to which approach should be selected in any given patient is dependent up patient preference and the availability and experience of the operator and institution at which the patient is being treated.
[Mh] Termos MeSH primário: Técnicas de Ablação
Procedimentos Cirúrgicos Cardíacos/métodos
Cardiomiopatia Hipertrófica/cirurgia
Septos Cardíacos/cirurgia
Miocárdio/patologia
[Mh] Termos MeSH secundário: Técnicas de Ablação/efeitos adversos
Técnicas de Imagem Cardíaca
Procedimentos Cirúrgicos Cardíacos/efeitos adversos
Cardiomiopatia Hipertrófica/diagnóstico
Cardiomiopatia Hipertrófica/genética
Cardiomiopatia Hipertrófica/patologia
Eletrocardiografia
Predisposição Genética para Doença
Septos Cardíacos/patologia
Septos Cardíacos/fisiopatologia
Hemodinâmica
Seres Humanos
Seleção de Pacientes
Fenótipo
Recuperação de Função Fisiológica
Fatores de Risco
Resultado do Tratamento
Função Ventricular
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1161/CIRCRESAHA.116.309348


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[PMID]:28912178
[Au] Autor:Braunwald E
[Ad] Endereço:From the TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. ebraunwald@partners.org.
[Ti] Título:Cardiomyopathies: An Overview.
[So] Source:Circ Res;121(7):711-721, 2017 Sep 15.
[Is] ISSN:1524-4571
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The nonischemic cardiomyopathies are a diverse group of cardiac disorders that frequently cause heart failure and death and are now recognized with increasing frequency. There has been substantial progress in the clinical recognition and understanding of the natural history of these conditions. Well-established and new techniques of cardiac imaging are also helpful in this regard. Basic scientists are elucidating the pathogenesis and pathobiology of individual cardiomyopathies. In this compendium, some of the most important advances in this field are reviewed. Scientific opportunities to enhance further collaborative research to accelerate progress are identified.
[Mh] Termos MeSH primário: Cardiomiopatias
[Mh] Termos MeSH secundário: Animais
Técnicas de Imagem Cardíaca
Procedimentos Cirúrgicos Cardíacos
Cardiomiopatias/diagnóstico
Cardiomiopatias/epidemiologia
Cardiomiopatias/genética
Cardiomiopatias/terapia
Predisposição Genética para Doença
Seres Humanos
Técnicas de Diagnóstico Molecular
Miocárdio/patologia
Fenótipo
Valor Preditivo dos Testes
Fatores de Risco
Resultado do Tratamento
Função Ventricular
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1161/CIRCRESAHA.117.311812


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[PMID]:28910373
[Au] Autor:Lorbeer R; Hetterich H; Strobl R; Schafnitzel A; Patscheider H; Schindler A; Müller-Peltzer K; Sommer W; Peters A; Meisinger C; Heier M; Rathmann W; Bamberg F; Grill E
[Ad] Endereço:Department of Radiology, University Hospital, LMU Munich, Munich, Germany.
[Ti] Título:Lack of association of MRI determined subclinical cardiovascular disease with dizziness and vertigo in a cross-sectional population-based study.
[So] Source:PLoS One;12(9):e0184858, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: We investigated the association between subclinical cardiovascular diseases assessed by MRI examination and symptoms of dizziness and vertigo in participants of a population-based sample. METHODS: Data from 400 participants (169 women) aged from 39 to 73 of a cross-sectional MRI sub-study of the "Kooperative Gesundheitsforschung in der Region Augsburg" (KORA) FF4 study from the south of Germany was used. MRI determined subclinical cardiovascular diseases include left and right ventricular structure and function as well as the presence of carotid plaque and carotid wall thickness. Cerebrum diseases include white matter lesions (WML) and cerebral microbleeds (CMB). The main outcomes of dizziness and vertigo were assessed by standardized interview. Logistic regression models were applied and adjusted odds ratios (OR) with 95% confidence intervals (CI) were provided. RESULTS: Lifetime and 12-month prevalence of dizziness and vertigo were 30% (95%CI 26% to 35%) and 21% (95%CI 17% to 26%) respectively in this sample. On multivariable analysis, cardiac and carotid measurements were not associated with dizziness and vertigo excluding orthostatic vertigo (20%, 95CI 16% to 24%). Only in male participants, there was a significant association between WML and the presence of dizziness and vertigo (OR = 2.95, 95%CI 1.08 to 8.07). There was no significant association of CMB with dizziness and vertigo. However, CMB and WML were tending to associate with a higher risk of dizziness and vertigo in the whole sample (CMB: OR = 1.48, 95%CI 0.70; 3.15; WML: OR = 1.71, 95%CI 0.80 to 3.67;), in persons with prediabetes and diabetes (WML: OR = 2.71, 95%CI 0.89 to 8.23) and in men with normal glucose metabolism (CMB: OR = 2.60, 95%CI 0.56 to 12.0; WML: OR = 3.08, 95%CI 0.58 to 16.5). CONCLUSIONS: In this sample of participants without manifest cardiovascular diseases, subclinical left and right ventricular function and carotid structure were consistently not associated with dizziness and vertigo. Subclinical cerebrum measurements, however, tend to increase the risk for dizziness and vertigo, especially in men and in persons with prediabetes or diabetes.
[Mh] Termos MeSH primário: Encefalopatias/diagnóstico por imagem
Doenças Cardiovasculares/diagnóstico por imagem
Tontura/epidemiologia
Imagem por Ressonância Magnética/métodos
Vertigem/epidemiologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Estudos Transversais
Feminino
Alemanha/epidemiologia
Seres Humanos
Modelos Logísticos
Masculino
Meia-Idade
Prevalência
Fatores de Risco
Função Ventricular
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170915
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184858


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[PMID]:28859079
[Au] Autor:Colman MA; Pinali C; Trafford AW; Zhang H; Kitmitto A
[Ad] Endereço:School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
[Ti] Título:A computational model of spatio-temporal cardiac intracellular calcium handling with realistic structure and spatial flux distribution from sarcoplasmic reticulum and t-tubule reconstructions.
[So] Source:PLoS Comput Biol;13(8):e1005714, 2017 Aug.
[Is] ISSN:1553-7358
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Intracellular calcium cycling is a vital component of cardiac excitation-contraction coupling. The key structures responsible for controlling calcium dynamics are the cell membrane (comprising the surface sarcolemma and transverse-tubules), the intracellular calcium store (the sarcoplasmic reticulum), and the co-localisation of these two structures to form dyads within which calcium-induced-calcium-release occurs. The organisation of these structures tightly controls intracellular calcium dynamics. In this study, we present a computational model of intracellular calcium cycling in three-dimensions (3-D), which incorporates high resolution reconstructions of these key regulatory structures, attained through imaging of tissue taken from the sheep left ventricle using serial block face scanning electron microscopy. An approach was developed to model the sarcoplasmic reticulum structure at the whole-cell scale, by reducing its full 3-D structure to a 3-D network of one-dimensional strands. The model reproduces intracellular calcium dynamics during control pacing and reveals the high-resolution 3-D spatial structure of calcium gradients and intracellular fluxes in both the cytoplasm and sarcoplasmic reticulum. We also demonstrated the capability of the model to reproduce potentially pro-arrhythmic dynamics under perturbed conditions, pertaining to calcium-transient alternans and spontaneous release events. Comparison with idealised cell models emphasised the importance of structure in determining calcium gradients and controlling the spatial dynamics associated with calcium-transient alternans, wherein the probabilistic nature of dyad activation and recruitment was constrained. The model was further used to highlight the criticality in calcium spark propagation in relation to inter-dyad distances. The model presented provides a powerful tool for future investigation of structure-function relationships underlying physiological and pathophysiological intracellular calcium handling phenomena at the whole-cell. The approach allows for the first time direct integration of high-resolution images of 3-D intracellular structures with models of calcium cycling, presenting the possibility to directly assess the functional impact of structural remodelling at the cellular scale.
[Mh] Termos MeSH primário: Sinalização do Cálcio/fisiologia
Cálcio/metabolismo
Ventrículos do Coração/citologia
Modelos Cardiovasculares
Retículo Sarcoplasmático/metabolismo
Função Ventricular/fisiologia
[Mh] Termos MeSH secundário: Animais
Simulação por Computador
Seres Humanos
Ovinos
Análise Espaço-Temporal
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
SY7Q814VUP (Calcium)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pcbi.1005714



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