Dispersion-based reentry: mechanism of initiation of ventricular tachycardia in isolated rabbit hearts

Abstract

The aim of the study was to determine whether facilitation of reentry by potassium-channel openers is related to dispersion of refractoriness and/or modification of anisotropic properties of ventricular myocardium. The dispersion of ventricular effective refractory period (VERP), longitudinal and transverse ventricular conduction velocities (θL and θT, respectively), and wavelength [λ = VERP × θ(L or T)] were studied in Langendorff-perfused left ventricular epicardium in 20 rabbits during infusion of incremental doses of levcromakalim or nicorandil. Dispersion of refractoriness was assessed using standard deviation of VERP mean (SD-VERP), dispersion index (DI; SD-VERP/mean VERP), and maximum dispersion (Dmax = VERPmax − VERPmin). Ventricular conduction velocities and anisotropic ratio were not modified, whatever the dose used. VERP and λ were significantly shortened at high concentrations of levcromakalim and nicorandil. At these doses, SD-VERP, DI, and Dmax were increased significantly. Analysis of ventricular tachycardia induction, performed using a high-resolution ventricular mapping system, confirmed that heterogeneity and shortening of VERP were factors inducing functional conduction block. Our data suggest that, in rabbit left ventricular epicardium, functional conduction block facilitating the occurrence of reentry could be initiated by shortening and, especially, by dispersion of refractoriness during infusion of potassium-channel openers.

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).…”

Analysis of T-Wave Morphology From the 12-Lead Electrocardiogram for Prediction of Long-Term Prognosis in Male US Veterans

“…[22][23][24][25] Searching for a noninvasive measurement of this substrate, body surface potential mapping proved successful 26 -29 but is impractical for wide clinical use. Measurement of QTd from the 12-lead surface ECG was proposed a decade ago 3 and was believed to provide a reasonably good reflection of the true myocardial heterogeneity of repolarization.…”

Functional differences between junctional and extrajunctional adrenergic receptor activation in mammalian ventricle

“…Although incompletely understood, one putative mechanism underlying this link is the development of spatial heterogeneity of myocardial action potential duration (APD) induced by a heightened sympathetic tone (15, 18,27,32). The resulting dispersion of ventricular repolarization facilitates reentrant VAs, which may degenerate into fibrillation and result in SCD (8,28).Prior studies have suggested that heterogeneous sympathetic innervation of the ventricles accounts for the spatial heterogeneities produced by sympathetic stimulation (18,22,23). Mantravadi et al (18) observed that sympathetic nerve stimulation reversed the sequence of ventricular repolarization, although this largely focused on the left ventricular free wall in an in vitro preparation.…”

“…Although incompletely understood, one putative mechanism underlying this link is the development of spatial heterogeneity of myocardial action potential duration (APD) induced by a heightened sympathetic tone (15, 18,27,32). The resulting dispersion of ventricular repolarization facilitates reentrant VAs, which may degenerate into fibrillation and result in SCD (8,28).…”