Electrotonic metabolism of pacemaker activity. Further biological and mathematical observations on the behavior of modulated parasystole.

Abstract

SUMMARY An in vitro biologic model of parasystole and a mathematical model of parasystole based on the phase-response relationships derived from the biologic model were used in tandem to further develop our understanding of the patterns of ectopic activity that might arise as a consequence of the interaction of two pacemakers across a zone of block. Superfusion of the central segment of a dog Purkinje fiber with an ion-free isotonic sucrose solution provided a narrow region of block. The modulation of pacemaker activity by electrotonic potentials transmitted across the area of block was shown to be importantly influenced by the position of the "ectopic" pacemaker relative to the site of block. Effects of repetitive electrotonic influences on a single pacemaker cycle, the degree of entrance block and capture of the pacemaker during a phase of supernormal excitability were also studied in both the biologic and mathematical models. Our results indicate that marked shifts in the incidence and pattern of manifest ectopic activity can occur as a result of slight changes in heart rate, ectopic pacemaker rate, level of block and the position of the parasystolic pacemaker relative to the block border.ELECTROTONIC POTENTIALS transmitted across an area of depressed conductivity may modulate the activity of a spontaneously beating pacemaker beyond the region of block. 1-3 Electrotonic depolarizations that occur early during phase 4 of the spontaneous pacemaker cycle delay the next discharge; those that occur later in the cycle accelerate, or "capture," the pacemaker.3 Thus, the activity of an ectopic focus, "protected" but not insulated by an area of depressed excitability, may be modulated by activity in the surrounding tissue according to a biphasic electrotonic influence or phase-response relationship.In a computer model programmed to imitate the modulation of an ectopic pacemaker, Moe and coworkers4 defined the patterns of entrainment and ectopic activity that may be expected to result from such interaction. Jalife and Moe' confirmed some of these predictions in a sucrose gap preparation of Purkinje tissue.Simplifying assumptions had been incorporated into the mathematical model, with the recognition that they would at least quantitatively warp the recorded patterns if not the basic rules of behavior: (1) made for supernormal excitability. In only a few runs was a relatively refractory period considered.In the present study, additional experiments were conducted in the sucrose gap preparation to assess the importance of these simplifications and to incorporate the biologic results into appropriately modified computer programs. Experiments were designed to test the effects of repetitive electrotonic influences on a single "ectopic" pacemaker cycle, the position of the ectopic pacemaker relative to the site of block, the degree of block between the two active segments and capture of the pacemaker during a phase of supernormal excitability. Methods Biologic ModelUnbranched free-running false tendons obtained from dog hear...

Morphology and electrophysiology of the mammalian atrioventricular node

“…The increase in A Vnodal transmission time with shortening of cycle length was due to "stagnation" between N and NH zone. This stagnation was likened to the mechanism of electrotonic transmission described for other cardiac tissues, where an inexcitable segment, interposed between two excitable regions, functions as a purely passive resistance-capacitance circuit (12,37,67,200). The stagnation is caused by cessation of active transmission at the inexcitable element, which can be crossed by electrotonic current bringing distal excitable ceUs to threshold.…”

“…A possible explanation for this phenomenon could be that during atrial fibrillation the lower AV node acts as an automatic focus, protected from supraventricular impulses, the N zone becoming "passive" during the rapid bombardment by fibrillatory impulses. These supraventricular impuls es can, however, by providing electrotonic currents, modulate the firing of the pacemaker (12). The random ventricular rhythm would then be the result of the random firing of the electrotonically modulated pacemaker.…”

“…Such a mechanism is, of course, completely speculative. If, on the other hand, the A V node does not delay conduction in the traditional sen se but acts as a nonprotected pacemaker (12,32,211), delay and protection may yet reside inside the A V node itself. However, without further data this mechanism is speculative as weil.…”

A Generalized Model of Active Media With a Set of Interacting Pacemakers: Application to the Heart Beat Analysis

“…can be modulated by current pulses stimulating (super-threshold depolarizing) applied extracellularly [Jalife & Moe, 1976;Sano et al, 1978;Jalife et al, 1980;Antzelevitch et al, 1982].…”

“…Experimentally obtained characteristics can be represented by a phase response curve (PRC) [Jalife & Moe, 1976;Antzelevitch et al, 1982;Reiner & Antzelevitch, 1985].…”