Abstract
Alternans of action potential duration has been associated with T wave alternans and the development of arrhythmias because it produces large gradients of repolarization. However, little is known about alternans dynamics in large mammalian hearts. Using optical mapping to record electrical activations simultaneously from the epicardium and endocardium of 9 canine right ventricles, we demonstrate novel arrhythmogenic complex spatiotemporal dynamics. (i) Alternans predominantly develops first on the endocardium. (ii) The postulated simple progression from normal rhythm to concordant to discordant alternans is not always observed; concordant alternans can develop from discordant alternans as the pacing period is decreased. (iii) In contrast to smaller tissue preparations, multiple stationary nodal lines may exist and need not be perpendicular to the pacing site or to each other. (iv) Alternans has fully three-dimensional dynamics and the epicardium and endocardium can show significantly different dynamics: multiple nodal surfaces can be transmural or intramural and can form concave/convex surfaces resulting in islands of discordant alternans. (v) The complex spatiotemporal patterns observed during alternans are very sensitive to both the site of stimulation and the stimulation history. Alternans in canine ventricles not only exhibit larger amplitudes and persist for longer cycle length regimes compared to those found in smaller mammalian hearts, but also show novel dynamics not previously described that enhance dispersion and show high sensitivity to initial conditions. This indicates some underlying predisposition to chaos and can help to guide the design of new drugs and devices controlling and preventing arrhythmic events.
Highlights
It is well known that increased dispersion of repolarization can lead to large variations in refractory period and conduction velocity that can, in turn, induce fibrillation (Han and Moe, 1964; Kuo et al, 1983)
In the first section we investigate whether alternans appears in a way similar to that of previous studies using smaller hearts and monolayers, after which we perform the first quantitative study of differences in alternans properties of the epicardium and endocardium by characterizing the onset and evolution of alternans on the two surfaces as a function of pacing frequency
In the fourth section we show that as cycle length is decreased in the larger tissues of canine ventricles, it is possible to convert from discordant alternans back to concordant and again to discordant alternans as the cycle length decreases, which can lead to separate regions of alternans with various degrees of complexity as a function of cycle length
Summary
It is well known that increased dispersion of repolarization can lead to large variations in refractory period and conduction velocity that can, in turn, induce fibrillation (Han and Moe, 1964; Kuo et al, 1983). This dynamics can develop into discordant alternans, where part of the tissue responds with a short APD, while another responds with a long APD (Pastore et al, 1999; Qu et al, 2000; Watanabe et al, 2001). There have been many studies quantifying the dynamics of alternans in space, they have all been conducted in monolayers (Shiferaw et al, 2005; Bien et al, 2006; Jia et al, 2007; Kim et al, 2007; de Diego et al, 2008; Weinberg et al, 2010) or small mammalian hearts (Pastore et al, 1999; Choi and Salama, 2000; Pastore and Rosenbaum, 2000; Walker et al, 2003; Hayashi et al, 2007; Mironov et al, 2008; Myles et al, 2008, 2011; Hsieh et al, 2009; Ziv et al, 2009)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
