Inhibition in the human heart.

Abstract

Subthreshold electrotonic depolarizations exerted inhibitory actions on impulse conduction and generation in isolated cardiac tissues. To determine whether inhibition occurs in human myocardium and to investigate the effects of time and voltage as well as distance on myocardial inhibition, 16 subjects were studied in the clinical electrophysiology laboratory by standard techniques. Atrial and ventricular pacing were performed with the use of a quadripolar catheter. The basic drive train (S1) and premature stimulus (S2) were introduced at the distal bipolar electrode pair through 1 current output generator and the subthreshold conditioning stimulus (Sc) was introduced before S2 at the distal or proximal bipolar pair through a separate current output generator. When Sc was initiated at the distal electrodes 40 ms before S2, inhibition of S2 could always be demonstrated (atrium or ventricle). Since Sc was introduced progressively earlier than S2, Sc inhibited the response to S2 according to a curvilinear strength-interval relationship; increasing mA of Sc from < 1.0-10.0 increased the interval at which Sc preceded S2 and still inhibited S2. With currents of Sc of 10.0 mA or less, Sc inhibited S2 in the ventricle (n = 11) and atrium (n = 5) when Sc preceded S2 by 40-160 ms (mean 85 ms) and 80-190 ms (mean 116 ms), respectively. Ventricular inhibition attempted with Sc at the proximal bipolar pair and S2 at the distal pair was successful in 3 of 9 patients. The effect of Sc on ventricular excitability threshold of S2 was determined in 3 patients. For all 3 patients the current threshold of S2 varied directly as a function of the magnitude of current used for Sc. Apparently, subthreshold stimuli can prevent subsequent threshold stimuli from depolarizing human atrium and ventricle, inhibition is both time and voltage dependent and inhibition is more effective if the inhibitory stimulus is applied close to the site of the threshold stimulus. Inhibition most likely occurs by Sc electronically affecting the response of the tissue to S2, possibly in part by modifying myocardial excitability threshold, thereby preventing S2 from initiating an active response.