A three-dimensional human atrial model with fiber orientation. Electrograms and arrhythmic activation patterns relationship

The most common sustained cardiac arrhythmias in humans are atrial tachyarrhythmias, mainly atrial fibrillation. Areas of complex fractionated atrial electrograms and high dominant frequency have been proposed as critical regions for maintaining atrial fibrillation; however, there is a paucity of data on the relationship between the characteristics of electrograms and the propagation pattern underlying them. In this study, a realistic 3D computer model of the human atria has been developed to investigate this relationship. The model includes a realistic geometry with fiber orientation, anisotropic conductivity and electrophysiological heterogeneity. We simulated different tachyarrhythmic episodes applying both transient and continuous ectopic activity. Electrograms and their dominant frequency and organization index values were calculated over the entire atrial surface. Our simulations show electrograms with simple potentials, with little or no cycle length variations, narrow frequency peaks and high organization index values during stable and regular activity as the observed in atrial flutter, atrial tachycardia (except in areas of conduction block) and in areas closer to ectopic activity during focal atrial fibrillation. By contrast, cycle length variations and polymorphic electrograms with single, double and fragmented potentials were observed in areas of irregular and unstable activity during atrial fibrillation episodes. Our results also show: 1) electrograms with potentials without negative deflection related to spiral or curved wavefronts that pass over the recording point and move away, 2) potentials with a much greater proportion of positive deflection than negative in areas of wave collisions, 3) double potentials related with wave fragmentations or blocking lines and 4) fragmented electrograms associated with pivot points. Our model is the first human atrial model with realistic fiber orientation used to investigate the relationship between different atrial arrhythmic propagation patterns and the electrograms observed at more than 43000 points on the atrial surface.This work was partially supported by the Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica, Ministerio de Ciencia e Innovacion of Spain (TEC2008-02090), by the Plan Avanza (Accion Estrategica de Telecomunicaciones y Sociedad de la Informacion), Ministerio de Industria Turismo y Comercio of Spain (TSI-020100-2010-469), by the Programa Prometeo 2012 of the Generalitat Valenciana and by the Programa de Apoyo a la Investigacion y Desarrollo de la Universitat Politecnica de Valencia (PAID-06-11-2002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Tobón Zuluaga, C.; Ruiz Villa, CA.; Heidenreich, E.; Romero Pérez, L.; Hornero, F.; Saiz Rodríguez, FJ. (2013). A three-dimensional human atrial model with fiber orientation. Electrograms and arrhythmic activation patterns relationship. PLoS ONE. 8(2):1-13. https://doi.org/10.1371/journal.pone.0050883S11382Ho SY, Sanchez-Quintana D, Anderson RH (1998) Can anatomy define electric pathways? In: International Workshop on Computer Simulation and Experimental Assessment of Electrical Cardiac Function, Lausanne, Switzerland. 77–86.Tobón C (2009) Evaluación de factores que provocan fibrilación auricular y de su tratamiento mediante técnicas quirúrgicas. Estudio de simulación. Master Thesis Universitat Politècnica de València.Ruiz C (2010) Estudio de la vulnerabilidad a reentradas a través de modelos matemáticos y simulación de la aurícula humana. Doctoral Thesis Universitat Politècnica de València.Tobón C (2010) Modelización y evaluación de factores que favorecen las arritmias auriculares y su tratamiento mediante técnicas quirúrgicas. Estudio de simulación. Doctoral Thesis Universitat Politècnica de València.Henriquez, C. S., & Papazoglou, A. A. (1996). Using computer models to understand the roles of tissue structure and membrane dynamics in arrhythmogenesis. Proceedings of the IEEE, 84(3), 334-354. doi:10.1109/5.486738Grimm, R. A., Chandra, S., Klein, A. L., Stewart, W. J., Black, I. W., Kidwell, G. A., & Thomas, J. D. (1996). Characterization of left atrial appendage Doppler flow in atrial fibrillation and flutter by Fourier analysis. American Heart Journal, 132(2), 286-296. doi:10.1016/s0002-8703(96)90424-xMaleckar, M. M., Greenstein, J. L., Giles, W. R., & Trayanova, N. A. (2009). K+ current changes account for the rate dependence of the action potential in the human atrial myocyte. American Journal of Physiology-Heart and Circulatory Physiology, 297(4), H1398-H1410. doi:10.1152/ajpheart.00411.200

A pilot study on ethanol-polyethylene glycol-formalin fixation of farm animal cadavers

Most embalming of cadavers for anatomical dissection in veterinary medicine has used 6-10% formaldehyde resulting in discoloured and rigid specimens. This project produced teaching specimens of sheep, horse and calf cadavers having their musculoskeletal and visceral structures with a natural appearance using a fixation solution with lowered concentrations of formaldehyde (2% and 3%) together with ethanol arid polyethylene glycols. Fixation parameters (palpable consistency, flexibility, colour, tissue hydration and odour) were assessed qualitatively by twice weekly dissections over two months for sheep and three months for horses and calf. Formaldehyde levels, measured in the breathing zone, were below the maximum allowable concentration in all specimens except for a 300 kg horse cadaver. To evaluate the effectiveness of the fixation solution in microbial inhibition, tissue samples were taken and analyzed for the presence of culturable aerobic and anaerobic bacteria, yeasts and moulds. Single colonies of Pseudomonas oryzihabitans, Chryseobacterium sp., Acinetobacter sp. were isolated from lungs, and Micrococcus sp. and Bacillus sp. were isolated from one muscle sample

Supplementary Material for: The Conundrum of Papillary Breast Lesions within the C3 Category

<b><i>Objectives:</i></b> To identify features that could define papillary ductal cell proliferation within the C3 category and to subcategorise papillary lesions into benign papillomas which can be managed conservatively and atypical/malignant papillary neoplasms which require surgical intervention. <b><i>Study Design:</i></b> A blind microscopic rescreen of all C3 cases was conducted. The corresponding histological outcome was compared with the cytology. Statistical analysis was performed using papillary versus non-papillary outcomes and benign versus atypical/malignant papillary lesions. In addition, macropapillary lesions (papilloma and encysted papillary carcinoma) were plotted against micropapillary ductal carcinoma in situ. <b><i>Results:</i></b> Two hundred thirty FNA cases reported as C3 included 72 papillary neoplasms (52 benign papillomas and 20 atypical/malignant papillary lesions). Features specific to papillary lesions within C3 include macropapillary fragments, complex sheets, palisading strips, cystic background, cohesion and a decreased nuclear-to-cytoplasmic ratio. Features favouring atypical/malignant papillary lesions include decreased numbers of bare bipolar nuclei, discohesion and a non-cystic background. These features are common to most breast malignancies; however, identification of papillary features often results in a downgraded diagnosis from C5. <b><i>Conclusions:</i></b> This study supports the ability to reliably identify papillary ductal cell proliferation within C3. Certain features can distinguish papillary lesions from other C3 pathologies. This separation is likely to be clinically useful as papillary lesions may require a different management approach

Supplementary Material for: The Microscopic Complexities of C3 in Breast Cytology

<b><i>Background:</i></b> Fine-needle aspiration (FNA) of difficult breast lesions often results in an atypical (C3) report. The assortment of outcomes generated by C3 reports varies widely, and this has given rise to different clinical management pathways. <b><i>Objective:</i></b> To identify and objectively assess microscopic features associated with atypical/C3 breast FNA cases. <b><i>Materials and Methods:</i></b> A total of 230 atypical breast FNAs were subjected to a blind microscopic rescreen using a range of robust qualitative and quantitative cytological criteria including cellularity, architectural qualities, cytomorphology and background features. A logistic regression with a receiver operating characteristic (ROC) curve and the resultant forward stepwise analysis were conducted to assess the results. This statistical testing was measured against malignant, benign proliferative and benign non-proliferative outcomes. <b><i>Results:</i></b> The malignant and benign proliferative outcomes showed a mixture of opposing protective and predictive individual cytological criteria. The stepwise analysis produced models demonstrating the best combination of individual cytological criteria for malignancy, proliferative and benign non-proliferative entities. In the malignancy model, discohesion, nuclear crowding within sheets, diminished numbers of bare bipolar nuclei and myoepithelial cells, the presence of tubules or necrosis and the absence of a cystic background were important features. The benign proliferative model suggested the same criteria but with the opposite implication and with the addition of several others, such as the presence of apocrine metaplasia, retained polarity and a speckled or coarse chromatin pattern. Age was a significant factor in malignant and proliferative outcomes. The benign non-proliferative stepwise analysis produced a model with fewer criteria (complex sheets, bare bipolar nuclei and a cystic background) limiting clinical application. <b><i>Conclusion:</i></b> Atypical/C3 breast cytology remains a legitimate reporting category. However, it is associated with a number of different histological outcomes. The incidence of the C3 category can be significantly reduced by controlling extrinsic factors and understanding the associated microscopic features