Effects of drive train stimulus intensity on ventricular refractoriness in humans

The strength-interval relation between the intensity of premature stimulus and the ventricular effective refractory period (VERP) has been well characterized. The effects of variation in the intensity of the basic drive train stimuli (S1) on VERP are not as well defined. This relation was studied in 44 patients undergoing clinically indicated electrophysiological study.

The outputs of two stimulus isolation units were connected in parallel, allowing the intensity of S1 to be varied independently of intensity of the extrastimulus (S2). To prevent confounding effects from cycle length change, continuous overdrive pacing was performed for 3 minutes before each measurement of VERP. The effect of S1 intensity on VERP was assessed in 24 patients with S2 intensity kept constant at twice threshold. VERP shortened from 232 +/- 19 msec at an S1 intensity of 1.5 times threshold to 219 +/- 20 msec at 5 mA and 211 +/- 19 msec at 10 mA (p less than 0.0001 for baseline versus 5 mA and for 5 mA versus 10 mA). Autonomic blockade with atropine and propranolol blunted but did not completely eliminate this effect. To assess whether the effect of S1 intensity on VERP was independent of S2 intensity, S2 strength-interval curves were generated in 10 patients at low (1.5 times threshold) and high (10 mA) S1 intensities. All portions of the strength-interval curve were shifted to the left by an increase in S1 intensity. The time course of change in VERP after an abrupt increase in S1 intensity was assessed in an additional 10 patients. VERP changed slowly, requiring 18 +/- 28 seconds to shorten by 2 msec and 64 +/- 46 seconds to decrease by 10 msec after a change in S1 intensity from 1.5 times threshold to 10 mA. In a final group of 10 patients, VERP was measured using an eight-beat drive train and a 4-second intertrain interval. With this more conventional protocol, VERP shortened by 14 +/- 8 msec with an increase in S1 intensity from 1.5 times threshold to 10 mA.

Increasing S1 intensity results in clinically significant, progressive shortening of VERP in man. This effect is independent of S2 intensity. The prolonged time course of the change in VERP after an increase in S1 intensity and the attenuation of this effect by autonomic blockade are consistent with stimulation of sympathetic nerve terminals and catecholamine release as a result of intense stimulation.