Subthreshold stimulation of Purkinje fibers interrupts ventricular tachycardia in intact hearts: Experimental study with voltage-sensitive dyes and imaging techniques

The effects of subthreshold stimulation (STS) delivered during right atrial pacing and ventricular tachycardia (VT) were investigated in Langendorff-perfused guinea pig hearts. The hearts were stained with a voltage-sensitive dye (RH 421) to map the propagation of optical action potentials. Sustained VT was reliably induced by 5-second trains (cycle length [CL], 25 to 50 milliseconds; duration, 0.5 to 10 milliseconds; and voltage, 2x threshold voltage) of impulses (n=12 hearts) or a single premature beat (n=6). The location of extrastimuli was not critical to the induction of VT, but the diameter of the heart had to be ≥14.5 mm. During VT, heart rate increased from 200 to 600 beats per minute; action potential durations decreased from 112 to 175 milliseconds to 60 to 105 milliseconds, with no diastolic interval. Activation on the epicardium spread anisotropically, but VT decreased the 'apparent' maximum conduction velocity (Θ(max)) by 68% and altered the orientation of the major axis from beat to beat. Activation patterns and (Θ(max)) measured during VT were similar to patterns recorded during direct pacing of the ventricle and indicated that Purkinje fibers no longer propelled ventricular excitation. STS (CL, 25 to 50 milliseconds; duration, 0.5 to 25 milliseconds; and voltage, 0.5x to 0.8x threshold; trains of 2.0 to 2.5 seconds) interrupted VT when applied to Purkinje fibers lining the endocardium (n=6) but failed to interrupt VT when applied to the epicardium (n=8). In atrial pacing, STS delivered to the endocardium increased Θ(max) from 2.44±0.32 (mean±SEM) to 3.63±0.21 m/s in a local region surrounding the first activation sites (n=4). Alternatively, VT could be terminated by reducing Θ(max) (≃55%) with procainamide (10 μmol/L) (n=6). STS terminates VT by synchronizing ventricular excitation most likely by increasing local conduction and/or improving the coupling between Purkinje and ventricular cells.