LABORATORY INVESTIGATION ELECTROPHYSIOLOGY Overdrive suppression of conduction at the canine Purkinj e-muscle junction

We have shown previously that overdrive suppression of conduction in depolarized His-Purkinje tissue requires conduction asymmetry. In this study we examined whether overdrive suppression of conduction can occur at the Purkinje-muscle junction, where natural asymmetry of conduction exists. Canine Purkinje-muscle preparations were superfused with hyperkalemic Tyrode's solution (KCl 8 to 12 mM), and action potentials were recorded from Purkinje, junctional, and muscle cells. Initially, the Purkinje fiber was paced at the shortest cycle length at which 1:1 anterograde Purkinje-muscle conduction occurred. The papillary muscle then was paced for 10 to 50 beats at shorter cycle lengths during which, because of conduction asymmetry at the Purkinje-muscle junction, 1: 1 retrograde muscle-Purkinje conduction also occurred. After overdrive papillary muscle pacing, Purkinje fiber pacing at the same cycle length that previously resulted in 1:1 conduction now produced transient Purkinje-muscle conduction block (overdrive suppression of conduction). The degree and duration of overdrive suppression of conduction were proportional to the rate and duration of overdrive pacing. After overdrive pacing, Purkinje cell action potential amplitude and Vmax recovered within 300 msec, yet conduction block persisted for up to 7 sec. In contrast, excitability in papillary muscle cells near the Purkinje-muscle junction increased continuously after overdrive pacing. These data suggest that rapid activation ofPurkinje cells during overdrive pacing was not required for overdrive suppression of conduction and that restoration of conduction after overdrive pacing was determined primarily by recovery of excitability in papillary muscle cells. Transient Purkinje-muscle conduction block after periods of rapid ventricular rates might account for overdrive-induced conduction disturbances normally attributed to bundle branch block. Circulation 76 No. 6, 1388-1396, 1987. SEVERAL CLINICAL and experimental studies have reported transient anterograde atrioventricular or bundle branch block after periods of rapid ventricular pacing. 'h6Recently the mechanism for this phenomenon, known as overdrive suppression of conduction, has been investigated in His-Purkinje tissue subjected to ischemia in vivo5 or to simulated ischemia in vitro.6 These studies suggest that rapid pacing produces a cumulative and rate-related depression of action potential amplitude and excitability in Purkinje cells that From the Krannert Institute of Cardiology, the Departments of Pharmacology and Toxicology and of Medicine, Indiana University School of Medicine, and the Roudebush Veterans Administration Medical Center, Indianapolis. Supported in part by the Herman C. Krannert Fund, Indianapolis; by grants HL-06308 and HL-07182 from the NHLBI, Bethesda, MD; by the Attorney General of Indiana Public Health Trust and the Roudebush Veterans Administration Medical Center, Indianapolis; and by a Grantin-Aid from the American Heart Association, Indiana Affiliate, Inc., Indianapolis. Address for correspondence: Robert F. Gilmour, Jr., Ph.D., Krannert Institute of Cardiology, Indiana University School of Medicine, 1100 West Michigan St., Indianapolis, IN 46223. Received April 14, 1987; revision accepted Sept. 3, 1987. 1388 may persist transiently when the pacing rate is slowed. Asymmetry of conduction in such preparations facilitates 1: 1 conduction at more rapid pacing rates during retrograde pacing than during anterograde pacing. Consequently, after a period of overdrive retrograde pacing, action potential amplitude and excitability may be reduced to such an extent that anterograde block occurs, even at slower pacing rates. The observation that conduction asymmetry contributes to the production of overdrive suppression of conduction in depressed His-Purkinje tissue suggests that overdrive suppression may occur in other tissues under conditions that promote conduction asymmetry. Therefore we investigated whether overdrive suppression of conduction occurred at the canine Purkinjemuscle junction, since numerous studies have shown that impulse transmission across Purkinje-muscle junctions occurs more readily retrogradely than anterogradely, particularly if the junction has been exposed to agents having negative dromotropic effects.7 '4 In addition, we investigated whether resumption of Purkinje-muscle conduction was associated with restoraCIRCULATION by gest on A ril 9, 2017 http://ciajournals.org/ D ow nladed from LABORATORY INVESTIGATION-ELECTROPHYSIOLOGY tion of Purkinje cell action potential amplitude and Vmaxor muscle cell excitability.