Modeling triggered cardiac activity: an analysis of the interactions between potassium blockade, rhythm pauses, and cellular coupling.
It is known that under certain conditions, a combination of potassium channel blockade, sympathetic nervous activity, and pauses in sinus rhythm can increase the occurrence of cardiac arrhythmias. Although the arrhythmogenic interactions of these three factors are not completely understood, it is believed that the associated arrhythmias may be initiated by afterpotentials via a process that we refer to as propagated triggered activity. Using a two-cell computational model of ventricular action potential kinetics, we simulate nonuniform potassium blockade, sympathetic nervous activity, and pauses in sinus rhythm under conditions of hypokalemia. Under these conditions, the two-cell model suggests that (1) the arrhythmogenic interactions of potassium blockade and sympathetic nervous activity are highly dependent on heart rate; (2) triggered activity induced by potassium blockade would most likely occur during a pause in sinus rhythm; (3) during a sufficiently large pause in sinus rhythm, potassium blockade can induce triggered activity at normal levels of sympathetic activity; and (4) potassium blockade can increase the probability of triggered activity only if heart rate falls within a critical range. We also show that during pauses in sinus rhythm, two-cell triggering interactions between potassium blockade and sympathetic activity closely parallel the parametric displacement of the dynamic instability underlying the afterpotentials. Our results indicate that the behavior of the triggering mechanism studied here is consistent with that of pause-induced arrhythmias.
Gibb
W J
WJ
Cardiovascular Research Institute, University of California, San Francisco/Berkeley, USA.
Wagner
M B
MB
Lesh
M D
MD
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology; D015220:Calcium Channels / Q000378:metabolism; D020746:Calcium Channels, L-Type; D006321:Heart / Q000503:physiopathology; D006801:Humans; D008433:Mathematics; D008955:Models, Cardiovascular; D026902:Potassium Channel Blockers; D013564:Sympathetic Nervous System / Q000503:physiopathology
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D026902:Potassium Channel Blockers