Chapter Multiscale Modeling of Myocardial Electrical Activity: From Cell to Organ

Endocrinolog

In silico ischaemia-induced reentry at the Purkinjeventricle interface

This computational modelling work illustrates the influence of hyperkalaemia and electrical uncoupling induced by defined ischaemia on action potential (AP) propagation and the incidence of reentry at the Purkinjeventricle interface in mammalian hearts. Unidimensional and bidimensional models of the Purkinjeventricle subsystem, including ischaemic conditions (defined as phase 1B) in the ventricle and an ischaemic border zone, were developed by altering several important electrophysiological parameters of the LuoRudy AP model of the ventricular myocyte. Purkinje electrical activity was modelled using the equations of DiFrancesco and Noble. Our study suggests that an extracellular potassium concentration [K](o) 14 mM and a slight decrease in intercellular coupling induced by ischaemia in ventricle can cause conduction block from Purkinje to ventricle. Under these conditions, propagation from ventricle to Purkinje is possible. Thus, unidirectional block (UDB) and reentry can result. When conditions of UDB are met, retrograde propagation with a long delay (320 ms) may re-excite Purkinje cells, and give rise to a reentrant pathway. This induced reentry may be the origin of arrhythmias observed in phase 1B ischaemia. In a defined setting of ischaemia (phase 1B), a small amount of uncoupling between ventricular cells, as well as between Purkinje and ventricular tissue, may induce UDBs and reentry. Hyperkalaemia is also confirmed to be an important factor in the genesis of reentrant rhythms, since it regulates the range of coupling in which UDBs may be induced.This work was supported: (i) by the European Commission preDiCT grant (DG-INFSO-224381), (ii) by the 'VI Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica' from the Ministerio de Economia y Competitividad of Spain (grant number TIN2012-37546-C03-01) and the European Commission (European Regional Development Funds - ERDF - FEDER), and (iii) by the Programa de Apoyo a la Investigacioon y Desarrollo (PAID-06-11-2002) de la Universidad Politecnica de Valencia, Programa Prometeo (PROMETEO/2012/030) de la Conselleria d'Educacio Formacio I Ocupacio, Generalitat Valenciana, and (iv) Direccion General de Politica Cientifica de la Generalitat Valenciana (GV/2013/119).Esteban Ramírez, J.; Saiz Rodríguez, FJ.; Romero Pérez, L.; Ferrero De Loma-Osorio, JM.; Trénor Gomis, BA. (2014). In silico ischaemia-induced reentry at the Purkinjeventricle interface. EP-Europace. 16(3):444-451. https://doi.org/10.1093/europace/eut386S44445116

Reoperación coronaria por toracotomía izquierda sin circulación extracorpórea después de laringuectomía: seguimiento a nueve años

The use of left thoracotomy is an alternative approach in redo coronary surgery in selected patients for whom median sternotomy is potentially hazardous. We present a patient in whom a redo reoperative coronary revascularization was performed off-pump via left thoracotomy to avoid a tracheal stoma. Nine years after reoperation the patient remains free of cardiac symptoms. In selected patients, redo coronary bypass grafting can be performed without cardiopulmonary bypass through a left thoracotomy, with a low perioperative morbidity and mortality rate and good long-term symptomatic improvement.La toracotomía izquierda es una vía de acceso alternativa en las reoperaciones coronarias en algunos enfermos en los cuales la reesternotomía puede ser peligrosa. Presentamos un enfermo en quien realizamos una reoperación coronaria sin circulación extracorpórea a través de una toracotomía izquierda para evitar una incisión quirúrgica en las proximidades de una traqueotomía permanente. Nueve años después el enfermo permanece asintomático. En casos seleccionados se pueden realizar reoperaciones coronarias sin circulación extracorpórea a través de una toracotomía izquierda con morbilidad y mortalidad bajas y con buenos resultados a largo plazo

Surgical treatment of aortobronchial fistula after thoracic endograft failure

Endovascular stent grafting has been recently considered as a less invasive alternative to either medical therapy or open surgical treatment for many patients with descending thoracic aortic disease. Late complications are rarely described in literature. Herein, we described the occurrence of an aorto-bronchial fistula and a retro-A dissection in a 73-year-old man after stent-grafting for a penetrating atherosclerotic ulcer (PAU) of the descending thoracic aorta and the successful surgical technique adopted in order to remove the stent-graft

Regulation of the Cardiac Na+/K+ ATPase by Phospholemman

Hansraj Dhayan, Rajender Kumar, Andreas Kukol, ‘Regulation of the Cardiac Na+/K+ ATPase by Phospholemman’, in Sajal Chakraborti, Naranjan Dhalla, eds., Regulation of Membrane Na+-K+ ATPase, (Switzerland: Springer, 2016), ISBN 978-3-319-24748-9, eISBN 978-3-319-24750-2.Peer reviewe

Tack energy and switchable adhesion of liquid crystal elastomers

The mechanical properties of liquid crystal elastomers (LCEs) make them suitable candidates for pressure-sensitive adhesives (PSAs). Using the nematic dumbbell constitutive model, and the block model of PSAs, we study their tack energy and the debonding process as could be measured experimentally in the probe-tack test. To investigate their performance as switchable PSAs we compare the tack energy for the director aligned parallel, and perpendicular to the substrate normal, and for the isotropic state. We find that the tack energy is larger in the parallel alignment than the isotropic case by over a factor of two. The tack energy for the perpendicular alignment can be 50% less than the isotropic case. We propose a mechanism for reversibly switchable adhesion based on the reversibility of the isotropic to nematic transition. Finally we consider the influence of several material parameters that could be used to tune the stress-strain response

Reduced response to IKr blockade and altered hERG1a/1b stoichiometryin human heart failure

Heart failure (HF) claims 250,000 lives per year in the US, and nearly half of these deaths are sudden and presumably due to ventricular tachyarrhythmias. QT interval and action potential (AP) prolongation are hallmark proarrhythmic changes in the failing myocardium, which potentially result from alterations in repolarizing potassium currents. Thus,we aimed to examinewhether decreased expression of the rapid delayed rectifier potassiumcurrent, IKr, contributes to repolarization abnormalities in human HF. Tomap functional IKr expression across the left ventricle (LV), we optically imaged coronary-perfused LV free wall from donor and end-stage failing human hearts. The LV wedge preparation was used to examine transmural AP durations at 80% repolarization (APD80), and treatment with the IKr-blocking drug, E-4031, was utilized to interrogate functional expression. We assessed the percent change in APD80 post-IKr blockade relative to baseline APD80 (ΔAPD80) and found that ΔAPD80s are reduced in failing versus donor hearts in each transmural region, with 0.35-, 0.43-, and 0.41-fold reductions in endo-, mid-, and epicardium, respectively (p = 0.008, 0.037, and 0.022). We then assessed hERG1 isoform gene and protein expression levels using qPCR and Western blot. While we did not observe differences in hERG1a or hERG1b gene expression between donor and failing hearts, we found a shift in the hERG1a:hERG1b isoform stoichiometry at the protein level. Computer simulations were then conducted to assess IKr block under E-4031 influence in failing and nonfailing conditions. Our results confirmed the experimental observations and E-4031-induced relative APD80 prolongationwas greater in normal conditions than in failing conditions, provided that the cellularmodel of HF included a significant downregulation of IKr. In humanHF, the response to IKr blockade is reduced, suggesting decreased functional IKr expression. This attenuated functional response is associated with altered hERG1a:hERG1b protein stoichiometry in the failing human LV, and failing cardiomyoctye simulations support the experimental findings. Thus, of IKr protein and functional expression may be important determinants of repolarization remodeling in the failing human LV.We thank the Translational Cardiovascular Biobank & Repository (TCBR) at Washington University for provision of donor/patient records. The TCBR is supported by the NIH/CTSA (UL1 TR000448), Children's Discovery Institute, and Richard J. Wilkinson Trust. We also thank the laboratory of Dr. Sakiyama-Elbert for the use of the StepOnePlus equipment We appreciate the critical feedback on the manuscript by Dr. Jeanne Nerbonne. This work has been supported by the National Heart, Lung & Blood Institute (NHLBI, R01 HL114395). K. Holzem has been supported by the American Heart Association (12PRE12050315) and the NHLBI (F30 HL114310).Holzem, KM.; Gómez García, JF.; Glukhov, AV.; Madden, EJ.; Koppel, AC.; Ewald, GA.; Trénor Gomis, BA.... (2016). Reduced response to IKr blockade and altered hERG1a/1b stoichiometryin human heart failure. Journal of Molecular and Cellular Cardiology. 96:82-92. https://doi.org/10.1016/j.yjmcc.2015.06.008S82929