The 'Second Factor' of tachycardia-induced atrial remodeling
Authors: R Tieleman
Journal: Cardiovascular Research (2000)

See article by Van der Velden et al. [6] ( pages 476 -ments by Wijffels el al. [1] revealed that the time courses 486) in this issue.of both processes were fairly different.Whereas after 2 days the atrial refractory period did not shorten any further, During recent years, atrial fibrillation (AF) research has AF only became persistent after 1-2 weeks.Wijffels et al. received increasing attention.One of the explanations for therefore discussed that other factors might have been this may be the ageing of the population with an increase important for the induction of persistent AF, such as in the prevalence of AF.Another important reason surely conduction slowing, structural changes with local conducis the discovery of AF-induced atrial electrical remodeling tion block or atrial dilatation [1].as originally described by Wijffels et al. [1] in their masterpiece article 'AF begets AF'.In this article the authors described the effects of automatic repetitive re- Conduction slowing and stabilisation of AF induction of AF by a 'fibrillation-pacemaker' on atrial electrophysiology in previously healthy, chronically in-The study by Van der Velden and colleagues [6] in this strumented goats.At the start of the protocol the induced issue of Cardiovascular Research is a direct follow-up of episodes of AF typically lasted just a few seconds after the original study by Wijffels et al. [1].Using a simplified which a new episode had to be induced automatically by fibrillation pacemaker in chronically instrumented goats, the pacemaker.However, with an increased duration of the they investigated the effects of various durations of stimulation protocol, the induced episodes prolonged until automatic repetitive induction of AF on the expression and eventually AF did not convert spontaneously anymore.distribution of the gap junction proteins connexin 40 They suggested that this was due to the progressive (CX40) and connexin 43 (CX43) in the atrial tissue of shortening of the atrial effective refractory period.Since goats.They described that with an increased duration of the atrial conduction velocity over Bachmann's bundle did pacing, the expression of CX40 decreased significantly, not change, the calculated wavelength decreased, which and the protein became more heterogeneously distributed.explained the increased propensity of the atria to fibrillate.The expression of CX 43 did not change.Both the CX40 / Importantly, they described that this process of atrial 43 immunofluorescence signal and the CX40 / 43 protein electrical remodeling was reversible within 1 week after ratios decreased with an increased duration of the stimularestoration of sinus rhythm, which offered a lot of potential tion protocol.By contrast, the mRNA levels of CX40 and for future improvement of anti-arrhythmic therapy in AF.CX43 remained unchanged, suggesting that the changes As a result, many studies on the process of atrial electrical occurred at a post-translational level, such as proteolysis.remodeling have been performed, investigating the cause Furthermore, in the present study the heterogeneity of of shortening of the refractory period [2], or evaluation of CX40 distribution correlated with the stabilization of AF the existence of electrical remodeling and its reversibility [6].As CX 40 is known to influence the conduction in humans with AF [3][4][5].properties of atrial tissue and the vulnerability for atrial However, close examination of the relationship between arrhythmias [7], it is logical that the authors concluded that the shortening of the atrial refractory period and the 'the time course of the changes in distribution and content prolongation of the induced episodes of AF in the experi-of CX40 gap junctional remodeling might be involved in the pathogenesis of sustained AF ' [6].In other words, the authors suggest that after completion of the early changes