Effect of anisotropy on ventricular vulnerability to unidirectional block and reentry by single premature stimulation during normal sinus rhythm in rat heart

Single high-intensity premature stimuli when applied to the ventricles during ventricular drive of an ectopic site, as in the Winfree's "pinwheel experiment", usually induce reentry arrhythmias in the normal heart, while single low-intensity stimuli barely do. Yet, ventricular arrhythmia vulnerability during normal sinus-rhythm remains largely unexplored. With a view to define the role of anisotropy on ventricular vulnerability to unidirectional conduction block and reentry, we revisited the pinwheel experiment with reduced constraints in the in situ rat heart. New features included single premature stimulation during normal sinus-rhythm, stimulation and unipolar potential mapping from the same high-resolution epicardial electrode array and progressive increase in stimulation strength and prematurity from diastolic threshold until arrhythmia induction. Measurements were performed with 1ms cathodal stimuli at multiple test-sites (n=26) in 7 rats. Stimulus induced virtual electrode polarization during sinus-beat recovery phase influenced premature ventricular responses. Specifically, gradual increase in stimulus strength and prematurity progressively induced make, break and graded response stimulation mechanisms. Hence, unidirectional conduction block occurred: along fiber direction, on right and left ventricular free walls (n=23), initiating figure-eight reentry (n=17) and tachycardia (n=12); across fiber direction, on lower interventricular septum (n=3), initiating spiral-wave reentry (n=2) and tachycardia (n=1). Critical time window (55.1±4.7ms, 68.2±6.0ms) and stimulus-strength lower limit (4.9±0.6mA) defined vulnerability to reentry. Novel finding of this study was that ventricular tachycardia evolves and is maintained by episodes of scroll-like wave and focal activation couplets. We also found that single low-intensity premature stimuli can induce repetitive ventricular response (n=13) characterized by focal activations.