Mechanism of ventricular vulnerability to single premature stimuli in open-chest dogs.

Abstract

To determine the mechanism of ventricular vulnerability to electrical stimulation, we simultaneously recorded from 120 transmural electrodes in a 35 X 20 X 5-mm portion of right ventricular infundibulum in seven dogs. Baseline pacing (S1) was performed from outside the mapped region followed by single premature stimulation (S2) of increasing strength at the center of the mapped region. In five of six episodes of ventricular fibrillation and 26 of 30 episodes of repetitive responses, complete reentrant pathways were observed. Earliest activation following S2 was not at the site of S2 stimulation but was at a point between the S1 and S2 sites of stimulation. Activation spread away from the early site toward the opposite side of the mapped region around the sides of an arc of block near the S2 site to form a "figure-of-eight." The activation fronts coalesced to activate the region around the S2 site last and, if the difference in times between activation at the early site and near the S2 site was large, reentered the tissue toward the S1 site. Ventricular refractory periods were determined in four dogs following S1 pacing; the regions with the greatest nonuniformity in the dispersion of refractoriness were not the regions of unidirectional block after S2 stimulation. Thus, 1) ventricular fibrillation and repetitive responses induced electrically with S1 and S2 stimuli at different ventricular sites arise by figure-of-eight reentry, 2) this reentry is caused by the ability of S2 stimulation both to prolong refractoriness near the S2 site and to initiate a propagated response in the region between the S1 and S2 sites, and 3) a nonuniform dispersion of refractoriness is not crucial for the electrical induction of reentry leading to ventricular fibrillation or repetitive responses when S1 and S2 stimuli are given at different locations on the right ventricular outflow tract.

Quasiperiodicity and chaos in cardiac fibrillation.

“…In the computer model (with the two-variable cell model), using the same stimulus protocol that induced reentry in the experimental preparations (12,13), single or paired spiral waves were readily induced ( Fig. 3 A ).…”

“…We adapted the right ventricular epicardial sheet preparation described by Davidenko et al (11), consisting of a 1-2 mm thick slice of right ventricular epicardium, ‫ف‬ 25 mm in length and width, pinned down in a chamber and superfused with oxygenated Tyrode's solution at 37 Њ C. Using an S1-S2 stimulation protocol similar to that used to induce ventricular fibrillation in the canine ventricle (12,13), a reentrant arrhythmia consistent with a persistent spiral wave was readily induced, but was very susceptible to spontaneous termination and could not be induced to break up into multiple reentrant wavefronts to simulate a fibrillation-like state. However, after treatment with the ATP-sensitive K ϩ -channel agonist cromakalim (5-10 M) to shorten the action potential duration by 30-50% and reduce wavelength commensurately, a fibrillationlike state could be induced.…”

“…An extracellular bipolar electrogram (0.5-mm interpole distance) was continuously recorded on tape and later digitized at 1 KHz and analyzed off line. Activation mapping was performed with a 509 bipolar electrode array (interpolar distance 0.5 mm, interelectrode distance 1.6 mm), using a computerized mapping system (E-Map, Auckland, NZ), as described previously (12,13).…”

Mechanism of origin of conduction disturbances in aging human atrial bundles: Experimental and model study

“…Most significantly, there was a response, which we have termed a conduction gate, that was selective in its direction, and such gating led to a shifted or reentrant pattern of subsequent excitation. In 1988 Chen et al [2][3][4] initiated a series of studies in ventricular muscle in which macroscopic repolarization gradients were induced by S 1 -S 2 stimuli at different locations. In the presence of macroscopic repolarization gradients, they found that the earliest site of excitation following early premature stimuli occurred consistently at a location between the S 1 and S 2 sites.…”

“…1 It is widely known that early premature stimuli initiate reentrant conduction disturbances in the presence of macroscopic gradients of repolarization. [2][3][4][5][6][7] In experimental analyses of these conduction disturbances, the repolarization gradients have been produced primarily by delivering a premature stimulus (S 2 ) at a location distal to the regular stimulus (S 1 ).2-4 Also, 1-D cable models of the associated sodium current events have used this two-stimulus arrangement to create repolarization gradients. 8 Here, all stimuli were given at a single site, so there was no macroscopic repolarization gradient induced by pacing first at one location and then at a second.…”