Abstract
Background: Circus type re-entry is classically associated with reduced action potential (AP) conduction velocity through partially refractory tissue resulting in unidirectional conduction block. We assessed the extent to which premature extrasystolic APs under such conditions resulted in ventricular arrhythmogenesis in isolated Langendorff-perfused murine hearts. Methods and Results: A novel programmed electrical stimulation (PES) protocol applied trains of 8 S1 stimuli at 100 ms intervals followed by extrasystolic S2 stimuli at successively decreasing S1S2 intervals. S2 stimulus strengths required to overcome refractoriness, reduce ventricular effective refractory period (VERP) and thereby elicit extrasystolic APs, increased with shortened S1S2 intervals, despite constant durations at 90% recovery (APD90) of the preceding APs. Critical interval, CI, the difference APD90-VERP, consequently increased with stimulus strength. The corresponding latencies and peak amplitudes of the extrasystolic APs consequently sharply increased and decreased respectively with CI thereby potentially replicating necessary conditions for re-entrant, circus-type, arrhythmia. The dependence of CI upon stimulus strength tended to consistent limiting values expected from approaches to absolute refractory periods. These values were greater in arrhythmogenic (mean CI 18.9±0.55 ms, n=4) than in non-arrhythmogenic hearts (mean CI 15.1±0.37, n=4; P=0.001, ANOVA), despite their statistically indistinguishable APD90 (arrhythmogenic hearts: 40.9±2.23 ms, n=4 vs non-arrhythmogenic hearts: 36.5±2.61ms, n=4; p>0.05, ANOVA) or VERP values (arrhythmogenic hearts: 22.5±2.66 ms, n=4 vs non-arrhythmogenic hearts: 21.8±2.53 ms, n=4; p>0.05, ANOVA). Conclusions: These findings suggest existence of a specific CI (CI∗) in turn corresponding to specific conditions of latency and action potential amplitude that would be sufficient to result in arrhythmogenesis.
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