THERAPY AND PREVENTION VENTRICULAR ARRYTHMIAS Summation and inhibition by ultrarapid train pacing in the human ventricle

Trains of ultrarapid stimuli that begin late in the refractory period have been reported both to produce early single captures to terminate tachyarrhythmias and to inhibit the response to subsequent threshold stimuli. To determine which characteristics of trains facilitate capture and which enhance inhibition, we compared the right ventricular strength interval relationship for single extrastimuli (S2) with that for 100 Hz trains with a duration of 100 msec in 29 patients. Pulse frequency was varied in 12 patients (50, 100, and 200 Hz) and train duration (50, 100, and 150 msec) was varied in 11 patients; the effect of procainamide (10.1 + 2.3 ,g/ml) was assessed in 10 patients. Relative to S2, 100 Hz trains with a duration of 100 msec prolonged the effective refractory period (ERP) at low current strength (inhibition), but shortened the ERP at high-current strength (summation): at 0.5 mA, the train ERP was 47 ± 6 (SEM) msec longer than the S2 ERP (p < .001); at 16 mA it was 12 ± 1 msec shorter (p < .001). Trains prolonged the functional refractory period (FRP) slightly at low currents (13 ± 3 msec, p = .001 at .05 mA), but did not shorten FRP significantly at high currents (2 ± 2 msec, p = NS at 16 mA) because of increased stimulus-response latency. Inhibition increased with increasing pulse frequency (p < .001), increasing train duration (p < .001), and procainamide (p < .01). Summation increased with increasing pulse frequency (p < .001), but not increasing train duration or procainamide, suggesting that inhibition and summation depend on different electrophysiologic mechanisms. We then compared trains and S2 during hemodynamically stable, monomorphic ventricular tachycardia at current strengths of twice threshold (20 tachycardias) and 10 mA (15 tachycardias). At twice threshold, trains prolonged the ERP by 55 ± 5 msec (p < .001) and the FRP by 25 ± 5 msec (p < .001). At 10 mA, they shortened the ERP by 13 ± 2 (p < .001), but did not alter the FRP. At twice threshold, inhibition prevented trains from terminating two tachycardias that could be terminated by S2. Our findings indicate that high-current, lowfrequency trains are best for single-capture termination of ventricular tachycardia. Circulation 76, No. 5, 1101-1109, 1987. SUBTHRESHOLD STIMULI during the refractory period have been reported both to inhibit and to facilitate the response to subsequent stimuli.'-8 In dogs, short trains of ultrarapid, subthreshold stimuli produce more inhibition than a single stimulus.3 In contrast, a train of three subthreshold stimuli, which did not produce depolarization when delivered alone or in pairs, has been reported to depolarize the human ventricle (summation).' A systemic investigation of the effects of repetitive stimulation during the refractory period on myocardial excitability has not been reported. The results of such a study are not only of basic interest but also have From the Cardiac Arrhythmia Unit, Stanford University Medical Center, Stanford, CA. Address for correspondence: Charles D. Swerdlow, M.D., Cardiac Arrhythmia Unit, Cardiology Division, CVRC 289, Stanford University Medical Center, 300 Pasteur Dr., Stanford, CA 94305. Received Dec. 11, 1986; revision accepted July 23, 1987. important clinical implications. Trains can cause single, earliest captures to terminate supraventricular or ventricular tachycardia without the time-consuming diastolic scanning necessary with single extrastimuli.9' 10 Alternatively, subthreshold trains that inhibit local activation have been reported to terminate ventricular tachycardia.1 In this study, we first investigated the effects of train stimulation on inhibition and summation in the human right ventricle during ventricular pacing. We studied the effect of varying current strength, train duration, and pulse frequency and the effect of procainamide. Then we applied our findings to termination of ventricular tachycardia.