Effects of Na(+) and K(+) channel blockade on vulnerability to and termination of fibrillation in simulated normal cardiac tissue.
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.
Qu
Zhilin
Z
David Geffen School of Medicine at UCLA, 47-123 CHS, 10833 Le Conte Ave., Los Angeles, CA 90095, USA. zqu@mednet.ucla.edu
Weiss
James N
JN
D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D003198:Computer Simulation; D006801:Humans; D008955:Models, Cardiovascular; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000502:physiology; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology*
D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D026941:Sodium Channel Blockers; D015222:Sodium Channels