Directional differences in excitability and margin of safety for propagation in sheep ventricular epicardial muscle.

Abstract

Computer simulations and isolated tissue experiments were used to characterize the relation between excitability and margin of safety for propagation in anisotropic ventricular myocardium. Longitudinal, uniform transverse, and nonuniform transverse tissue directions were modeled in a one-dimensional Beeler-Reuter based cable. Stimulation threshold was smallest in the nonuniform transverse direction. The safety factor for propagation was determined in the model as the total axial charge that was available for depolarizing downstream tissue divided by the threshold charge that was just sufficient for continued propagation and was largest in the longitudinal direction. The strength-interval plot for the junction between simulated longitudinal and nonuniform transverse directions identified a range of stimulus strengths and intervals that resulted in nonuniform transverse but not longitudinal propagation. When high values of transverse resistance were used, higher stimulus strengths during premature stimulation resulted in longitudinal but not nonuniform transverse propagation. The experimental strength interval plots from 17 L-shaped preparations of isolated sheep epicardial muscles had similar characteristics. In nine additional L-shaped tissue experiments, changing extracellular K' concentration from 4 to 20 mM resulted in progressive membrane depolarization and conduction impairment in both directions. However, in eight of nine experiments, complete block occurred first in the transverse direction. In one experiment, block was simultaneous in both directions. We conclude that, under normal conditions, threshold requirements for active propagation are lower for transverse than for longitudinal propagation. In addition, when active membrane properties are impaired, the safety factor for propagation is Larger in the direction along the longitudinal axis of the cells. (Circulation Research 1990;67:97-110) A ction potential propagation in the heart is a complex function determined by the electrical properties associated with cell excitability,"2 as well as by the degree of cell-to-cell communication and the geometrical arrangements of intercellular connections.3,4 Moreover, conduction velocity in cardiac muscle is faster along the longitudinal (L) axis of the cells than along the transverse (T) axis.5-7 The

Anisotropic Conduction Properties in Canine Atria Analyzed by High-Resolution Optical Mapping

“…Some studies 1,10,11 showed that longitudinal propagation was more vulnerable to block under conditions to reduce the excitability of cardiac cells, while others 8,9,12,13 showed that transverse block preferentially occurred. The safety of conduction depends on the curvature of wave fronts and on the electrical coupling between the cells.…”

“…[1][2][3][4] This anisotropic characteristic of propagation, which is defined by cell shapes and cell packing architecture 1,2 and by the expression and distribution of gap junctions, 5,6 has been a matter of great concern to cardiologists, because it may set the stage for the reentry of excitation, leading to life-threatening tachyarrhythmias. [7][8][9] Unidirectional conduction block is known to occur in association with tissue anisotropy, but there are conflicting results about whether longitudinal 1,10,11 or transverse block 8,9,12,13 preferentially occurs. We hypothesized that the preferential direction of conduction block might be altered in association with age-dependent changes in the structural anisotropy.…”

Mechanism of Procainamide-Induced Prevention of Spontaneous Wave Break During Ventricular Fibrillation

“…Other factors, such as tissue anatomy, including tissue thickness, 12 cellular coupling, 17,18 and tissue anisotropy, 19,20 might also exert an influence on the causation of source-sink mismatch and subsequent wave break. However, the demonstration of PA-induced prevention of spontaneous wave break at a site where spontaneous breakup occurred before exposure to drug ( Figure 4B) suggests that drug-induced prevention of APD shortening per se played a decisive role in causing spontaneous wave break in the present study.…”

Anisotropic conduction block and reentry in neonatal rat ventricular myocyte monolayers

“…On the other hand, Koura et al (15) reported that preferential longitudinal block in young tissue converted to preferential transverse block with aging. Finally, whereas interventions that decreased Na current availability in anisotropic tissue caused preferential longitudinal conduction block in some studies (7,31), other studies showed preferential transverse block under low excitability conditions (7,16).A unified mechanistic interpretation of these findings is made difficult by differences in pacing protocols, animal models, and methods. Some studies used premature extrastimulus testing (S1S2 pacing) to induce conduction block, whereas others used incremental rapid pacing (8,30,31).…”

“…Spach et al (31) showed that anisotropy can lead to preferential longitudinal conduction block initiating reentry, due to a lower safety factor for longitudinal than transverse conduction. Other investigators, however, found preferential transverse conduction block in anisotropic tissue (7,8,22,24,26), particularly when gap junction conductance was pharmacologically decreased by heptanol (8). Although theoretical mechanisms for both preferential longitudinal block (due to reduced safety factor) (27, 31) and preferential transverse block [due to reduced gap junction conductance (13) and certain low excitability conditions (8)] have been proposed, the experimental evidence for these mechanisms in intact three-dimensional (3D) tissue is somewhat conflicting.…”