The transient outward potassium current plays a key role in spiral wave breakup in ventricular tissue

Abstract

Spiral wave reentry as a mechanism of lethal ventricular arrhythmias has been widely demonstrated in animal experiments and recordings from human hearts. It has been shown that in structurally normal hearts, spiral waves are unstable, breaking up into multiple wavelets via dynamical instabilities. However, many of the second-generation action potential models give rise only to stable spiral waves, raising issues regarding the underlying mechanisms of spiral wave breakup. In this study, we carried out computer simulations of two-dimensional homogeneous tissues using five ventricular action potential models. We show that the transient outward potassium current (Ito), although it is not required, plays a key role in promoting spiral wave breakup in all five models. As the maximum conductance of Ito increases, it first promotes spiral wave breakup and then stabilizes the spiral waves. In the absence of Ito, speeding up the L-type calcium kinetics can prevent spiral wave breakup, however, with the same speedup kinetics, spiral wave breakup can be promoted by increasing Ito. Increasing Ito promotes single-cell dynamical instabilities, including action potential duration alternans and chaos, and increasing Ito further suppresses these action potential dynamics. These cellular properties agree with the observation that increasing Ito first promotes spiral wave breakup and then stabilizes spiral waves in tissue. Implications of our observations to spiral wave dynamics in the real hearts and action potential model improvements are discussed.

Why Is Only Type 1 Electrocardiogram Diagnostic of Brugada Syndrome? Mechanistic Insights From Computer Modeling

“…In a previous study, 16 we showed that I to could destabilize spiral wave reentry, causing spiral wave breakup. Here, we show that the late I to stabilizes reentry and can prevent the spiral wave breakup caused by the peak I to .…”

“…Besides suppressing the genesis of P2R, late I to can also prevent spiral wave breakup. We showed in a previous study 16 that I to could promote spiral wave breakup by steepening the APD restitution curves. Besides the steep APD restitution-induced breakup, we also observed P2Rs resulting from the complex wave dynamics, giving rise to a mixture of spontaneous firings (P2Rs) and spiral wave reentry (Figure S7 and Videos S3 and S4).…”

“…The mechanisms that I to promotes spiral wave instabilities have been investigated in our previous study. 16 Figure 4B shows voltage snapshots for the same G to values with γ=0.2, and the spiral waves were all stable. In Figure 4C, we show the spiral wave cycle length (CL) versus γ for the 2 G to values (1.5 and 3.2 mS/cm 2 ) that gave rise to spiral wave breakup in Figure 4A, showing that increasing γ stabilized the spiral wave reentry, that is, the CL became less variable and finally constant as γ was large enough.…”

Impact of Combined Modulation of Two Potassium Ion Currents on Spiral Waves and Turbulent States in the Heart

“…They found that these suppressions led to different alterations in APD [ 38 ]. Additionally, Landaw et al demonstrated through multiple simulation models the significant influence of the transient outward potassium current in initiating the fragmentation of spiral waves [ 40 ]. Therefore, it can be deduced that alterations in various potassium ion currents in different models lead to varying effects on the formation of spiral waves and turbulent states.…”

Analysis and simulation of a modified cardiac cell model givesaccurate predictions of the dynamics of the original one

“…The (endocardial) TP06 cardiac cell model [14], which is based on the TNNP04 model [15], is by now a well-established and much studied cardiac cell model [9][10][11][12][13]16]. Despite that, a Email address: andre.erhardt@wias-berlin.de (André H. Erhardt) rigorous mathematical analysis of all its dynamics is still lacking.…”