RESUMO
Rheumatoid arthritis (RA) is a progressive disease that affects both pediatric and adult populations. The cellular basis for RA has been investigated extensively using animal models, human tissues and isolated cells in culture. However, many aspects of its aetiology and molecular mechanisms remain unknown. Some of the electrophysiological principles that regulate secretion of essential lubricants (hyaluronan and lubricin) and cytokines from synovial fibroblasts have been identified. Data sets describing the main types of ion channels that are expressed in human synovial fibroblast preparations have begun to provide important new insights into the interplay among: (i) ion fluxes, (ii) Ca2+ release from the endoplasmic reticulum, (iii) intercellular coupling, and (iv) both transient and longer duration changes in synovial fibroblast membrane potential. A combination of this information, knowledge of similar patterns of responses in cells that regulate the immune system, and the availability of adult human synovial fibroblasts are likely to provide new pathophysiological insights.
Assuntos
Fibroblastos/fisiologia , Animais , Fenômenos Eletrofisiológicos , Humanos , Canais Iônicos/fisiologia , Membrana Sinovial/citologiaRESUMO
BACKGROUND: Nasal polyposis (NP) is considered a subgroup within chronic rhinosinusitis. NP can be further subdivided into aspirin sensitive- and aspirin tolerant types (ASNP/ ATNP). Although the true etiology of NP has not been identified so far, it is agreed that NP represents an inflammatory disease of the nasal mucosa. Alterations of cellular kinase activities including that of IKK-2 might play a role in this inflammatory process. METHODS: Paraffin sections of ASNP, ATNP and controls were immunostained with Phospho-IkB-α antibody that detects the direct IKK-2 product (IkB-α. Intensity of epithelial staining was analysed semi-quantitatively by two independent observers. In cultured nasal polyp epithelial cells (NPECs) epithelial derived cytokines IL-8 and GRO α were induced by TNF-α or Staphylococcal supernatants and subsequently repressed by IKK-2 inhibitor TPCA-1. RESULTS: Significant Phospho-IkB-α staining was observed in the nasal epithelium of ASNP compared to ATNP and controls suggesting strong IKK-2 activation in patients with ASNP in vivo. In vitro, pro-inflammatory cytokines IL-8 and GRO-α in NPECs were significantly repressed by TPCA-1. CONCLUSION: IKK-2 activity is increased in the subgroup of ASNP. IL-8 and GRO-α responses were repressed by IKK-2 inhibitor TPCA-1 in vitro. IKK-2 inhibitors might represent a potential target for anti-inflammatory intervention in ASNP.
Assuntos
Amidas/farmacologia , Mucosa Nasal/patologia , Pólipos Nasais/metabolismo , Tiofenos/farmacologia , Adulto , Idoso , Quimiocina CXCL1/efeitos dos fármacos , Feminino , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Interleucina-8/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismoRESUMO
BACKGROUND: Staphylococcus aureus has been associated with chronic rhinosinusitis with nasal polyps (CRSwNP) pathogenesis but its role is still controversially discussed. Here, we demonstrate S. aureus detection in the mucosa of CRSwNP. In addition, intracellular residency of S. aureus in nasal polyp epithelial cells (NPECs) and its capability to induce TH-2 cytokines were analyzed in vitro. METHODS: Staphylococcus aureus detection in CRSwNP (n = 25), CRS without polyps (CRSsNP, n = 5), and turbinate mucosa (TM, n = 10) was performed by peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) and microbial cultivation from tissue biopsies. Intracellular residency was examined by intracellular persistence assay and electron microscopy. IL-6 and IL-13 responses to S. aureus infection and supernatants were quantified by ELISA. RESULTS: Peptide nucleic acid-fluorescence in situ hybridization positive bacterial cells were significantly increased in the epithelium of CRSwNP (17/25) compared to CRSsNP (0/5) and TM (1/10). Good concordance of PNA-FISH results and S. aureus cultivation was found applying Cohen's κ for CRSwNP (κ = 0.841) and TM (κ = 1.0). Intracellular persistence assay with S. aureus strain Newman and its corresponding small-colony variant mutant strain III33 demonstrated intracellular survival and replication of S. aureus within NPECs. Both S. aureus strains significantly induced IL-6 but not IL-13 in infected NPECs and in NPECs challenged with corresponding staphylococcal supernatants. CONCLUSION: Invasion of the epithelium by S. aureus was a phenomenon seen predominantly in CRSwNP. Regardless of an intra- or extracellular localization in the epithelium, S. aureus is capable to induce IL-6 synthesis in vitro and thus may contribute to the TH-2 cytokine pattern in CRSwNP.
Assuntos
Interleucina-6/biossíntese , Mucosa Nasal/microbiologia , Pólipos Nasais/microbiologia , Rinite/microbiologia , Sinusite/microbiologia , Infecções Estafilocócicas/complicações , Adulto , Células Cultivadas , Doença Crônica , Feminino , Humanos , Hibridização in Situ Fluorescente , Interleucina-13/biossíntese , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/imunologia , Pólipos Nasais/complicações , Pólipos Nasais/imunologia , Rinite/complicações , Rinite/imunologia , Sinusite/complicações , Sinusite/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologiaRESUMO
Systemic disorders represent a heterogenous group of diseases which can primarily manifest at the nose and sinuses as limited disease or secondarily as part of the systemic involvement. Rhinologists therefore play an important role in the diagnostic but also therapeutic process. Although therapy of systemic disorders is primary systemic, additional nasal surgery may become necessary. Surgical procedures include sinus surgery for the treatment of complications of the orbit and the lacrimal duct, septorhinoplasty due to saddle nose deformity and closure of septal perforation. Since many systemic disorders represent very rare diseases, recommendations are based on the analysis of single case reports and studies with a limited number of patients. Even though data is still limited, experiences published so far have shown that autogenous cartilage or bone transplants can be used in nasal reconstruction of deformities caused by tuberculosis, leprosy, wegener's granulomatosis, sarcoidosis and relapsing polychondritis. Experiences gained from these diseases support our observation that well-established techniques of septorhinoplasty can be used in systemic disorders as well. However, reaching a state of remission is an essential condition before considering any rhinosurgery in these patients. Under these circumstances revision surgery has to be expected more frequently compared to the typical collective of patients undergoing septorhinoplasty. These observations in part may also be useful for the treatment of nasal septal perforations since implantation of cartilage- or bone grafts represents an essential step in the closure of septal perforations. Apart from the treatment of orbital complications, sinus surgery has been proven beneficial in reducing nasal symptoms and increasing quality of life in patients refractory to systemic treatment.
Assuntos
Doenças Nasais/etiologia , Doenças Nasais/cirurgia , Doenças dos Seios Paranasais/etiologia , Doenças dos Seios Paranasais/cirurgia , Rinoplastia/métodos , Diagnóstico Diferencial , Endoscopia , Humanos , Septo Nasal/cirurgia , Deformidades Adquiridas Nasais/etiologia , Deformidades Adquiridas Nasais/cirurgia , Doenças Nasais/diagnóstico , Doenças dos Seios Paranasais/diagnóstico , Equipe de Assistência ao Paciente , Prognóstico , Qualidade de VidaRESUMO
Velocity of electrical conduction in cardiac tissue is a function of mechanical strain. Although strain-modulated velocity is a well established finding in experimental cardiology, its underlying mechanisms are not well understood. In this work, we summarized potential factors contributing to strain-velocity relationships and reviewed related experimental and computational studies. We presented results from our experimental studies on rabbit papillary muscle, which supported a biphasic relationship of strain and velocity under uni-axial straining conditions. In the low strain range, the strain-velocity relationship was positive. Conduction velocity peaked with 0.59 m/s at 100% strain corresponding to maximal force development. In the high strain range, the relationship was negative. Conduction was reversibly blocked at 118+/-1.8% strain. Reversible block occurred also in the presence of streptomycin. Furthermore, our studies revealed a moderate hysteresis of conduction velocity, which was reduced by streptomycin. We reconstructed several features of the strain-velocity relationship in a computational study with a myocyte strand. The modeling included strain-modulation of intracellular conductivity and stretch-activated cation non-selective ion channels. The computational study supported our hypotheses, that the positive strain-velocity relationship at low strain is caused by strain-modulation of intracellular conductivity and the negative relationship at high strain results from activity of stretch-activated channels. Conduction block was not reconstructed in our computational studies. We concluded this work by sketching a hypothesis for strain-modulation of conduction and conduction block in papillary muscle. We suggest that this hypothesis can also explain uni-axially measured strain-conduction velocity relationships in other types of cardiac tissue, but apparently necessitates adjustments to reconstruct pressure or volume related changes of velocity in atria and ventricles.
Assuntos
Sistema de Condução Cardíaco/fisiologia , Mecanotransdução Celular , Modelos Cardiovasculares , Contração Miocárdica/fisiologia , Animais , Músculos Papilares/fisiologia , CoelhosRESUMO
BACKGROUND: Bacterial etiology of chronic rhinosinusitis (CRS) still remains controversial. Whereas Staphylococcus aureus enterotoxins have been detected in CRS, the impact of Staphylococcus epidermidis, a major commensal inhabitant of the nose, has not been studied. Among others, serine and cysteine proteases have been identified as factors of virulence in S. epidermidis. METHODS: S. epidermidis was examined in tissue biopsies of 30 CRS patients (16 with nasal polyposis) using standard procedures. Primary human nasal epithelial cells from inferior nasal turbinates (HNECs), from nasal polyps (NPECs) and A549 airway epithelial cells were stimulated with S. epidermidis supernatants DSM20044 or ATCC35984 and the IL-8 and GRO-alpha response was quantified by ELISA. Protease-triggered chemokine responses and involvement of NF-kappaB were investigated by addition of protease or NF-kappaB inhibitors. Activation of NF-kappaB was demonstrated by quantitative DNA binding assay. RESULTS: S. epidermidis was the most frequently isolated bacteria in the majority of CRS patients. HNECs and NPECs revealed no different IL-6 and IL-8 synthesis following stimulation with DSM20044 or ATCC35984. Stimulation of HNECs and A549 cells with S. epidermidis supernatants resulted in increased IL-8 and GRO-alpha expression which could be suppressed by the serine protease inhibitor AEBSF and the NF-kappaB inhibitor BAY 11 but not by the cysteine protease inhibitor E64. Results obtained for A549 cells were similar to HNECs. CONCLUSION: S. epidermidis was present in the majority of CRS specimens. Proinflammatory impact of S. epidermidis supernatants on nasal epithelial cells was demonstrated by serine protease-triggered and NF-kappaB-dependent chemokine responses.
Assuntos
Quimiocina CXCL1/imunologia , Interleucina-8/imunologia , Mucosa Nasal/imunologia , Rinite/microbiologia , Sinusite/microbiologia , Staphylococcus epidermidis/imunologia , Linhagem Celular , Células Cultivadas , Doença Crônica , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Humanos , Interleucina-6/imunologia , NF-kappa B/antagonistas & inibidores , Mucosa Nasal/citologia , Pólipos Nasais/imunologia , Pólipos Nasais/microbiologia , Nitrilas/farmacologia , Rinite/imunologia , Inibidores de Serina Proteinase/farmacologia , Sinusite/imunologia , Staphylococcus epidermidis/isolamento & purificação , Sulfonas/farmacologiaRESUMO
The transverse tubular system (t-system) of ventricular cardiomyocytes is essential for efficient excitation-contraction coupling. In cardiac diseases, such as heart failure, remodeling of the t-system contributes to reduced cardiac contractility. However, mechanisms of t-system remodeling are incompletely understood. Prior studies suggested an association with altered cardiac biomechanics and gene expression in disease. Since fibrosis may alter tissue biomechanics, we investigated the local microscopic association of t-system remodeling with fibrosis in a rabbit model of myocardial infarction (MI). Biopsies were taken from the MI border zone of 6 infarcted hearts and from 6 control hearts. Using confocal microscopy and automated image analysis, we quantified t-system integrity (ITT) and the local fraction of extracellular matrix (fECM). In control, fECM was 18 ± 0.3%. ITT was high and homogeneous (0.07 ± 0.006), and did not correlate with fECM (R2 = 0.05 ± 0.02). The MI border zone exhibited increased fECM within 3 mm from the infarct scar (30 ± 3.5%, p < 0.01 vs control), indicating fibrosis. Myocytes in the MI border zone exhibited significant t-system remodeling, with dilated, sheet-like components, resulting in low ITT (0.03 ± 0.008, p < 0.001 vs control). While both fECM and t-system remodeling decreased with infarct distance, ITT correlated better with decreasing fECM (R2 = 0.44) than with infarct distance (R2 = 0.24, p < 0.05). Our results show that t-system remodeling in the rabbit MI border zone resembles a phenotype previously described in human heart failure. T-system remodeling correlated with the amount of local fibrosis, which is known to stiffen cardiac tissue, but was not found in regions without fibrosis. Thus, locally altered tissue mechanics may contribute to t-system remodeling.
Assuntos
Ventrículos do Coração/patologia , Infarto do Miocárdio/patologia , Estresse Mecânico , Animais , Fenômenos Biomecânicos , Matriz Extracelular/metabolismo , Fibrose , Masculino , Miócitos Cardíacos/patologia , CoelhosRESUMO
Microstructural characterization of cardiac tissue and its remodeling in disease is a crucial step in many basic research projects. We present a comprehensive approach for three-dimensional characterization of cardiac tissue at the submicrometer scale. We developed a compression-free mounting method as well as labeling and imaging protocols that facilitate acquisition of three-dimensional image stacks with scanning confocal microscopy. We evaluated the approach with normal and infarcted ventricular tissue. We used the acquired image stacks for segmentation, quantitative analysis and visualization of important tissue components. In contrast to conventional mounting, compression-free mounting preserved cell shapes, capillary lumens and extracellular laminas. Furthermore, the new approach and imaging protocols resulted in high signal-to-noise ratios at depths up to 60 µm. This allowed extensive analyzes revealing major differences in volume fractions and distribution of cardiomyocytes, blood vessels, fibroblasts, myofibroblasts and extracellular space in control vs. infarct border zone. Our results show that the developed approach yields comprehensive data on microstructure of cardiac tissue and its remodeling in disease. In contrast to other approaches, it allows quantitative assessment of all major tissue components. Furthermore, we suggest that the approach will provide important data for physiological models of cardiac tissue at the submicrometer scale.
Assuntos
Ventrículos do Coração , Imageamento Tridimensional , Miocárdio , Remodelação Ventricular , Animais , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Vasos Coronários/fisiopatologia , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Microscopia Confocal , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Miofibroblastos/metabolismo , Miofibroblastos/patologia , CoelhosAssuntos
Sinusite Maxilar/diagnóstico , Nasofaringite/diagnóstico , Otite Externa/diagnóstico , Otite Média Supurativa/diagnóstico , Tuberculose/diagnóstico , Antituberculosos/uso terapêutico , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Humanos , Sinusite Maxilar/tratamento farmacológico , Pessoa de Meia-Idade , Nasofaringite/tratamento farmacológico , Otite Externa/tratamento farmacológico , Otite Média Supurativa/tratamento farmacológico , Otoscopia , Tomografia Computadorizada por Raios X , Tuberculose/tratamento farmacológico , Tuberculose Pulmonar/diagnósticoRESUMO
Interleukin-16 is a soluble ligand to the CD4 molecule with chemotactic properties for CD4+ cells and a competence growth factor for CD4+ T cells, upregulating HLA-DR and the interleukin-2 receptor CD25. There is also evidence for a synergistic effect of interleukin-16 and interleukin-2 on the activation of CD4+ T cells. The infiltrate in mycosis fungoides, the most common cutaneous T cell lymphoma, is typically CD4+. We tested the possibility that interleukin-16 is involved in the formation and progression of these lesions. By reverse transcription-polymerase chain reaction, interleukin-16 mRNA was detected in 18 of 18 mycosis fungoides lesions investigated. By competitive reverse transcription-polymerase chain reaction, interleukin-16 mRNA expression increased with disease stage. Secreted interleukin-16 was detected by enzyme-linked immunosorbent assay in both Th1- and Th2-like T cell clones (as characterized by their production of interferon-gamma and interleukin-4) grown from lesional dermis and epidermis. By immunohistochemistry and in situ hybridization, infiltrating lymphocytes were the main producers of interleukin-16 whereas keratinocytes and endothelial cells remained negative. Atypical cells with convoluted nuclei were also positive. In advanced mycosis fungoides stages, many blast-like cells were positive, but some larger blasts remained negative. Interleukin-16 expression correlated positively with the expression of interleukin-2 and its receptor CD25 in individual skin lesions. Interleukin-2 expression, however, was weak or absent in samples from uninvolved skin, healthy controls and lesional psoriasis. Given the biologic properties of interleukin-16 and the parallel activation of the interleukin-2/CD25 pathway, interleukin-16 might be involved in the recruitment and stimulation of CD4+ lymphocytes in mycosis fungoides lesions and therefore contribute to the perpetuation of the associated cutaneous inflammation.
Assuntos
Linfócitos T CD4-Positivos/metabolismo , Interleucina-16/biossíntese , Micose Fungoide/imunologia , Neoplasias Cutâneas/imunologia , Linfócitos T CD4-Positivos/química , Linfócitos T CD8-Positivos/metabolismo , Humanos , Imuno-Histoquímica , Interleucina-16/análise , Interleucina-16/genética , Interleucina-2/análise , RNA Mensageiro/análise , Receptores de Interleucina-2/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/químicaRESUMO
Knowledge of the distribution of electrical fields in the human body is of importance for scientists, engineers and physicians. This paper shows one way to achieve this knowledge by numerical calculation based on macroscopic models of the human body. An anatomical model is created by preprocessing, segmentation and classification of the digital images within the Visible Man data set. Conductivity models are derived, which describe the distribution of electrical conductivity in the human body. A conductivity model is applied to solve an exemplary forward problem in electrophysiology, which consist of the calculation of the electrical field distribution arising from cardiac sources. The cardiac sources are obtained by a model of the excitation process within the heart. The calculation of electrical fields is carried out numerically by employing the finite difference method.
Assuntos
Anatomia Transversal , Condutividade Elétrica , Coração/diagnóstico por imagem , Coração/fisiologia , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
Simulations of the electro-mechanical behavior of the heart improve the comprehension of the mechanisms of the cardiovascular system. In this study a left ventricular model including electrical excitation and force development is presented. The electrical model consists of a complex electrophysiological cell model and a monodomain excitation diffusion model. The force development bases on the intracellular calcium concentration and is calculated with a force model. It consists--like the electrophysiological model--of non-linear coupled differential equations. Simulations are obtained in a realistic and anisotropic model of the left ventricle of the Visible Female data set provided by the National Library of Medicine, USA. Effects to the mechanical behavior will be examined in future.
Assuntos
Anatomia Transversal , Eletrocardiografia , Contração Miocárdica/fisiologia , Função Ventricular Esquerda/fisiologia , Canais de Cálcio/fisiologia , Simulação por Computador , Feminino , Sistema de Condução Cardíaco/fisiologia , Humanos , Modelos Teóricos , Células Musculares/fisiologia , Dinâmica não Linear , Ramos Subendocárdicos/fisiologiaRESUMO
Knowledge concerning passive mechanic cardiac properties is necessary to model behavior of whole hearts. Commonly, a continuum mechanics based description is chosen in conjunction with the finite element method. The aim of this work is to summarize, derive and evaluate hyperelastic material laws for inhomogeneous, anisotropic myocardium. Hence, different material laws were set up and their parameters were determined taking measurement data in literature into account. The material laws were compared from a theoretical and numerical point of view. Furthermore, the application of continuum mechanics based methods is evaluated concerning aspects of numerical solution and spatial discretisation. In further work the laws will be implemented and integrated in an existing software environment, which allows the calculation of deformations in complex geometries.
Assuntos
Análise de Elementos Finitos , Coração/fisiologia , Contração Miocárdica/fisiologia , Anisotropia , Fenômenos Biomecânicos , Simulação por Computador , Elasticidade , Humanos , Modelos Cardiovasculares , Análise Numérica Assistida por ComputadorRESUMO
Models of the cellular force development simulate the contractive behavior of the sarcomere. In conjunction with electrophysiological models they can contribute to a better comprehension of physiology and pathologies. Aim of this study is to examine the coupling of cellular electrophysiological processes and force development. For that a graphical user interface was developed to simplify the parameterization and calculation of the models as well as to present the results graphically. A feedback mechanism is introduced to pay attention to close connections between force development and intracellular processes. On basis of various tests with different boundary conditions, new force models are developed, parameterized, validated and compared with models in literature. In future studies the results will be tested in multiple cell organization.
Assuntos
Simulação por Computador , Eletrocardiografia , Sistema de Condução Cardíaco/fisiologia , Modelos Cardiovasculares , Contração Miocárdica/fisiologia , Sarcômeros/fisiologia , Actinas/fisiologia , Trifosfato de Adenosina/fisiologia , Canais de Cálcio/fisiologia , Gráficos por Computador , Humanos , Miosinas/fisiologia , Tropomiosina/fisiologia , Troponina/fisiologiaRESUMO
Computer simulations to reconstruct the transmembrane potential distribution were performed for an anisotropic finite element model of the heart. Transmembrane potential was reconstructed in the form of 3D patches. Test patterns generated with a cellular automaton were used. Tikhonov 0-order and 2-order reconstruction techniques were compared. Tikhonov 2-order regularization was shown to deliver better solutions; this is demonstrated by the inspection of the source space of the inverse problem and by the comparison of the correlation coefficients between the reconstructed and original distributions. Time information was incorporated into the regularization.
Assuntos
Simulação por Computador , Eletrocardiografia , Análise de Elementos Finitos , Sistema de Condução Cardíaco/fisiologia , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Modelos Cardiovasculares , Mapeamento Potencial de Superfície Corporal , Gráficos por Computador , Humanos , Modelos TeóricosRESUMO
Computer models of the heart can improve the understanding of the electrophysiological processes in healthy and diseased heart. They become more and more important for detailed diagnosis of arrhythmias and for optimization of therapy. Models of myocardium cells known today are described--they are based on the properties of all relevant ion channels in the cell membrane. Then it is demonstrated, how many cells can be joined to form a cell patch and how finally the complete heart can be modelled. A simpler approach is using a so called cellular automation that allows for a significant reduction of calculation time while sacrificing some accordance to reality. Adaptive cellular automations allow for a fast simulation with acceptable accuracy. Using them some results were gained for the simulation of typical arrhythmias, in the field of validation using an animal model and for therapy planning with RF-ablation.
Assuntos
Arritmias Cardíacas/fisiopatologia , Simulação por Computador , Eletrocardiografia , Sistema de Condução Cardíaco/fisiopatologia , Arritmias Cardíacas/diagnóstico , Diagnóstico por Computador , Humanos , Modelos CardiovascularesRESUMO
Computer aided simulations of the heart provide knowledge of phenomena, which are commonly neither visible nor measurable with current techniques. This knowledge can be applied e.g. in cardiologic diagnosis and therapy. A variety of models was created to reconstruct cardiac processes, e.g. electrical propagation and force development. In this work different macroscopic models were compared, i.e. models based on excitation-diffusion equations and cellular automata. The comparison was carried out concerning reconstruct-ability of cardiac phenomena, mathematical and biophysical foundation as well as computational expense. Particularly, the reconstruct-ability of electromechanic feedback mechanisms was examined. Perspectives for further developments and improvements of models were given.
Assuntos
Simulação por Computador , Eletrocardiografia , Coração/fisiologia , Modelos Cardiovasculares , Contração Miocárdica/fisiologia , Animais , Fenômenos Biofísicos , Biofísica , Sistema de Condução Cardíaco/fisiologia , Humanos , Modelos Teóricos , Dinâmica não LinearRESUMO
Models of cardiac tissue electrophysiology are an important component of the Cardiac Physiome Project, which is an international effort to build biophysically based multi-scale mathematical models of the heart. Models of tissue electrophysiology can provide a bridge between electrophysiological cell models at smaller scales, and tissue mechanics, metabolism and blood flow at larger scales. This paper is a critical review of cardiac tissue electrophysiology models, focussing on the micro-structure of cardiac tissue, generic behaviours of action potential propagation, different models of cardiac tissue electrophysiology, the choice of parameter values and tissue geometry, emergent properties in tissue models, numerical techniques and computational issues. We propose a tentative list of information that could be included in published descriptions of tissue electrophysiology models, and used to support interpretation and evaluation of simulation results. We conclude with a discussion of challenges and open questions.
Assuntos
Eletrofisiologia Cardíaca/métodos , Coração/fisiologia , Modelos Cardiovasculares , Potenciais de Ação/fisiologia , Animais , Fenômenos Fisiológicos Celulares , Previsões , Humanos , Miocárdio/citologia , CoelhosRESUMO
Cardiac experimental electrophysiology is in need of a well-defined Minimum Information Standard for recording, annotating, and reporting experimental data. As a step towards establishing this, we present a draft standard, called Minimum Information about a Cardiac Electrophysiology Experiment (MICEE). The ultimate goal is to develop a useful tool for cardiac electrophysiologists which facilitates and improves dissemination of the minimum information necessary for reproduction of cardiac electrophysiology research, allowing for easier comparison and utilisation of findings by others. It is hoped that this will enhance the integration of individual results into experimental, computational, and conceptual models. In its present form, this draft is intended for assessment and development by the research community. We invite the reader to join this effort, and, if deemed productive, implement the Minimum Information about a Cardiac Electrophysiology Experiment standard in their own work.