Reentrant and nonreentrant mechanisms contribute to arrhythmogenesis during early myocardial ischemia: results using three-dimensional mapping.

Abstract

The present study assessed the mechanisms responsible for the initiation and maintenance of premature ventricular complexes (PVCs) and ventricular tachycardia (VT) during early ischemia using a unique computerized mapping system capable of recording simultaneously from 232 individual intramural sites. In the chloralose-anesthetized cat, during normal sinus rhythm prior to ischemia, ventricular activation was rapid with a total activation time of 25 +/- 2 msec. Five minutes after occlusion of the left anterior descending (LAD) coronary artery, activation was delayed during sinus rhythm (64 +/- 6 msec) (p less than 0.001 vs. control) and was characterized by slow conduction in the same plane and block in both the same plane and in the endocardial-to-epicardial direction. In 76% of cases (16 of 21), initiation of single PVCs and the first beat of VT occurred through intramural reentry. In all but one case, initiation occurred in the subendocardium, adjacent to the site of delayed subendocardial and midmyocardial activation of the preceding sinus beat. The activation time of the sinus beat preceding the PVC or VT was significantly prolonged (149 +/- 7 msec, p less than 0.001 vs. sinus beats during ischemia not followed by a PVC or VT) with most of the delayed activity occurring in the subendocardium and midmyocardium, a finding that would not have been apparent by epicardial mapping alone. The length of the reentrant pathway ranged from 1.8-3.0 cm. Marked delay was a necessary, but not a sufficient, condition for reentry to occur since, in some cases, delays as large as 220 msec was found without initiation of reentry or the occurrence of nonreentrant PVCs or VT. Maintenance of VT by intramural reentry arose in either the subendocardium or the subepicardium and was primarily dependent on the continued presence of marked transmural delay (159 +/- 8 msec). In contrast, in 24% of cases (5 of 21), initiation of the first beat of VT arose in either the subendocardium or subepicardium by a mechanism other than reentry as evidenced by the lack of intervening electrical activity between the end of the preceding sinus beat and the initiation of the ectopic beat. The preceding sinus beat was characterized by delay (129 +/- 12 msec) comparable to that of sinus beats preceding reentrant ectopic beats (p = NS), but the marked delay was distant from the site of nonreentrant initiation. Ventricular tachycardia could be initiated by one mechanism (reentrant or nonreentrant) and maintained or terminated by another mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)

Functional Interactions between Distinct Sodium Channel Cytoplasmic Domains through the Action of Calmodulin

“…These simulations suggest that Ca 2ϩ -dependent as well as drug-dependent modulation of Na ϩ channel inactivation could critically influence conduction during oxidative stress. Heterogeneities in the action potential duration, coupled with conduction velocity changes could lead to marked dispersion of repolarization and unidirectional conduction block, especially in the ischemic myocardium and border zone, a substrate that favors the development of re-entrant arrhythmias (39,40).…”

Oxidative Mediated Lipid Peroxidation Recapitulates Proarrhythmic Effects on Cardiac Sodium Channels

“…[31][32][33][34] This strongly suggests that the generation of free radicals in the myocardium can induce an arrhythmic substrate, but the downstream underlying mechanisms have not been fully elucidated. Although functional changes have been described in multiple ion channels and transporters, Na ϩ channel dysfunction appears to play a key role under these conditions: Arrhythmias in the remodeled ischemic myocardium often evolve from sites of slow conduction near the border zone, 35 which displays rate-dependent slowing and facilitated reentry because of Na ϩ channel blockade. In the 5-day healing infarcted heart, cells of the EBZ show post- Figure 2C, inset.…”

Antiarrhythmic properties of tedisamil (KC8857), a putative transient outward K+ current blocker

“…Re-entry and abnormal automaticity are arrhythmogenic mechanisms which differ in their response to different drugs (Pogwizd & Corr, 1987;Brugada, 1987;Gitant & Cohen, 1988). An increase in refractoriness may be antiarrhythmic by selectively abolishing re-entry or, alternatively, by reducing the time available for arrhythmias.…”