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Effects of Na⁺ and K⁺ channel blockade on vulnerability to and termination of fibrillation in simulated normal cardiac tissue

¹Cardiovascular Research Laboratory and Departments of ²Medicine (Cardiology) and ³Physiology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California

Submitted 14 March 2005 ; accepted in final form 1 June 2005

Na⁺ and K⁺ channel-blocking drugs have anti- and proarrhythmic effects. Their effects during fibrillation, however, remain poorly understood. We used computer simulation of a two-dimensional (2-D) structurally normal tissue model with phase I of the Luo-Rudy action potential model to study the effects of Na⁺ and K⁺ channel blockade on vulnerability to and termination of reentry in simulated multiple-wavelet and mother rotor fibrillation. Our main findings are as follows: 1) Na⁺ channel blockade decreased, whereas K⁺ channel blockade increased, the vulnerable window of reentry in heterogeneous 2-D tissue because of opposing effects on dynamical wave instability. 2) Na⁺ channel blockade increased the cycle length of reentry more than it increased refractoriness. In multiple-wavelet fibrillation, Na⁺ channel blockade first increased and then decreased the average duration or transient time (<T_s>) of fibrillation. In mother rotor fibrillation, Na⁺ channel blockade caused peripheral fibrillatory conduction block to resolve and the mother rotor to drift, leading to self-termination or sustained tachycardia. 3) K⁺ channel blockade increased dynamical instability by steepening action potential duration restitution. In multiple-wavelet fibrillation, this effect shortened <T_s> because of enhanced wave instability. In mother rotor fibrillation, this effect converted mother rotor fibrillation to multiple-wavelet fibrillation, which then could self-terminate. Our findings help illuminate, from a theoretical perspective, the possible underlying mechanisms of termination of different types of fibrillation by antiarrhythmic drugs.

arrhythmias; antiarrhythmic drugs; simulation

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