Effects of persistent atrial fibrillation-induced electrical remodeling on atrial electro-mechanics – insights from a 3D model of the human atria

A 3D electromechanical model of the human atria was developed to investigate the effects of AFER on atrial electro-mechanics. Simulations were carried out in 3 conditions for 4states: (i) the control condition, representing the normal tissue (state 1) and the tissue 2–3months after cardio version (state 2) when the atrial tissue recovers its electrophysiological properties after completion of reverse electrophysiological remodelling; (ii) AFER-SR condition for AF-remodelled tissue with normal sinus rhythm (SR) (state 3); and (iii) AFER-AF condition for AF-remodeled tissue with re-entrant excitation waves (state 4). Our results indicate that at the cellular level, AFER (states 3 & 4) abbreviated action potentials and reduced the Ca2+content in the sarcoplasmic reticulum, resulting in a reduced amplitude of the intracellular Ca2+transient leading to decreased cell active force and cell shortening as compared to the control condition (states 1 & 2). Consequently at the whole organ level, atrial contraction in AFER-SR condition (state 3) was dramatically reduced. In the AFER-AF condition (state 4) atrial contraction was almost abolished

Reflexivity, the picturing of selves, the forging of methods

This paper addresses alternative models for a reflexive methodology and examines the ways in which doctoral students have appropriated these texts in their theses. It then considers the indeterminate qualities of those appropriations. The paper offers a new account of reflexivity as 'picturing', drawing analogies from the interpretation of two very different pictures, by Velázquez and Tshibumba. It concludes with a more open and fluid account of reflexivity, offering the notion of 'signature', and drawing on the work of Gell and also Deleuze and Guattari in relation to the inherently specific nature of 'concepts' situated in space and time

Multi-scale sensible heat fluxes in the urban environment from large aperture scintillometry and eddy covariance

Sensible heat fluxes (QH) are determined using scintillometry and eddy covariance over a suburban area. Two large aperture scintillometers provide spatially integrated fluxes across path lengths of 2.8 km and 5.5 km over Swindon, UK. The shorter scintillometer path spans newly built residential areas and has an approximate source area of 2-4 km2, whilst the long path extends from the rural outskirts to the town centre and has a source area of around 5-10 km2. These large-scale heat fluxes are compared with local-scale eddy covariance measurements. Clear seasonal trends are revealed by the long duration of this dataset and variability in monthly QH is related to the meteorological conditions. At shorter time scales the response of QH to solar radiation often gives rise to close agreement between the measurements, but during times of rapidly changing cloud cover spatial differences in the net radiation (Q*) coincide with greater differences between heat fluxes. For clear days QH lags Q*, thus the ratio of QH to Q* increases throughout the day. In summer the observed energy partitioning is related to the vegetation fraction through use of a footprint model. The results demonstrate the value of scintillometry for integrating surface heterogeneity and offer improved understanding of the influence of anthropogenic materials on surface-atmosphere interactions

Comparison of Atrial Fibrillation in the Young versus That in the Elderly: A Review

The incidence and prevalence of atrial fibrillation (AF) are projected to increase significantly worldwide, imposing a significant burden on healthcare resources. The disease itself is extremely heterogeneous in its epidemiology, pathophysiology, and treatment options based on individual patient characteristics. Whilst ageing is well recognised to be an independent risk factor for the development of AF, this condition also affects the young in whom the condition is frequently symptomatic and troublesome. Traditional thinking suggests that the causal factors and pathogenesis of the condition in the young with structurally normal atria but electrophysiological “triggers” in the form of pulmonary vein ectopics leading to lone AF are in stark contrast to that in the elderly who have AF primarily due to an abnormal substrate consisting of fibrosed and dilated atria acting in concert with the pulmonary vein triggers. However, there can be exceptions to this rule as there is increasing evidence of structural and electrophysiological abnormalities in the atrial substrate in young patients with “lone AF,” as well as elderly patients who present with idiopathic AF. These reports seem to be blurring the distinction in the pathophysiology of so-called idiopathic lone AF in the young versus that in the elderly. Moreover with availability of improved and modern investigational and diagnostic techniques, novel causes of AF are being reported thereby seemingly consigning the diagnosis of “lone AF” to a rather mythical existence. We shall also elucidate in this paper the differences seen in the epidemiology, causes, pathogenesis, and clinical features of AF in the young versus that seen in the elderly, thereby requiring clearly defined management strategies to tackle this arrhythmia and its associated consequences

Role of up-regulation of IK1 in action potential shortening associated with atrial fibrillation in humans

Objectives: Although previous studies in dogs have indicated a minimal role for changes in IK1 in the shortening of action potential duration (APD) associated with atrial fibrillation (AF), in humans, there is evidence for significant AF-induced up-regulation of this current. In this computer model study, we investigated the relative contributions of the remodeling of IK1, L-type calcium current, and other remodeled ionic channel currents to AF-induced APD reduction in human atrium. \ud \ud Methods: Two computer models of electrical activity of human atrial cell were modified by incorporating experimental data of AF-induced changes in human atrial ionic channel conductance and kinetics reported by Bosch et al. (ICaL, Ito, IK1, and INa) (AF-1) and Workman et al. (ICaL, Ito, and IK1) (AF-2). The roles and relative importance of individually remodeled ion channels in the APD reduction in human atrium were evaluated by the removal and exclusive methods, in which remodeling of specific currents was omitted, or considered in isolation, in the two models. \ud \ud Results: When tested together, previously reported AF-induced changes in sarcolemmal ion currents result in marked shortening of atrial APD90. With the AF-1 remodeled parameters, there is a 62% reduction in APD90 for the Nygren et al. model, and a 68% reduction for the Courtemanche et al. model, which are comparable to experimental results of 60% reduction seen in humans. When tested individually, AF-1-induced changes in ICaL, IK1, or Ito alone result in APD90 reduction of 20%, 64%, and –10%, respectively, for the Nygren et al. model, and 27%, 40%, and 11.6%, respectively, for the Courtemanche et al. model. With the AF-2 remodeled parameters, there is a 47% reduction in APD90 for the Nygren et al. model and a 49% reduction for the Courtemanche et al. model, which are also comparable to experimental results of 45% reduction. When tested individually, AF-2-induced changes in ICaL or IK1 alone result in APD90 reduction of 20% and 40%, respectively, for the Nygren et al. model, and 14% and 21%, respectively, for the Courtemanche et al. model. \ud \ud Conclusion: Previously reported changes in L-type Ca2+ current are insufficient to account for the observed reduction in atrial APD associated with persistent AF. Up-regulation of IK1 has a greater influence on atrial APD in the human model