Electrophysiologic properties and ventricular fibrillation in normal and myopathic hearts

Abstract

This study tests the hypothesis that moderate myocardial dysfunction is associated with altered myocardial anisotropic properties and structurally altered ventricular fibrillation (VF). Mongrel dogs were randomized to either a control group or a group that was rapidly paced at 250 beats/min until the left ventricular ejection fraction was < or = 40%. Changes in anisotropic properties and the electrical characteristics of VF associated with the development of moderate myocardial dysfunction were assessed by microminiature epicardial mapping studies. In vivo conduction, refractory periods, and repolarization times were prolonged in both longitudinal and transverse directions in myopathic animals versus controls. VF was different in myopathic versus control animals. There were significantly more conducted deflections during VF in normal hearts compared with myopathic hearts. Propagated deflection-to-deflection intervals during VF were significantly longer in myopathic hearts compared with controls (125.5 +/- 49.06 versus 103.4 +/- 32.9 ms, p = 0.009). There were no abnormalities in cell size, cell shape, or the number of intercellular gap junctions and there was no detectable change in the expression of the gap junction proteins Cx43 and Cx45. Moderate myocardial dysfunction is associated with significant electrophysiological abnormalities in the absence of changes in myocardial cell morphology or intercellular connections, suggesting a functional abnormality in cell-to-cell communication.

Gap Junction Blockers Decrease Defibrillation Thresholds Without Changes in Ventricular Refractoriness in Isolated Rabbit Hearts

“…Changes in passive membrane properties thus may prolong wavelength even though conduction velocity is slowed. These potential effects of cellular uncoupling by exogenous agents are in contrast to the relationship between heterogeneous uncoupling and defibrillation in models of cardiomyopathy 30,31 in which DFTs are increased. In the latter models, however, there is fibrosis and cellular disarray, which provide a substrate for disordered conduction independent of alteration in gap junction function.…”

Suppression of Ventricular Arrhythmias After Myocardial Infarction by AT1 Receptor Blockade: Role of the AT2 Receptor and Casein Kinase 2/Kir2.1 Pathway

“…For example in the rapid-pacinginduced heart failure rabbit model, reduced inward-rectifier K + (IK1) current occurs without decrease in Kir2.1 mRNA level, implying that the reduced current results from posttranslational modification of the channel protein [10]. In the rapid-pacing-induced heart failure dog model, moderate myocardial dysfunction was associated with significant electrophysiological abnormalities and VF, but no changes in myocardial cell morphology or intercellular connections, or expression of gap junction proteins connexin43 and connexin45, suggesting a dominant functional abnormality in cell-to-cell communication [20]. In the isolated perfused dog heart, spatiotemporal resolution mapping of optical transmembrane potentials detected erupting rotors that emit reentrant waves during early VF, and Bevolved^or deteriorated into a pattern lacking the spatiotemporal features of epicardial rotors [21].…”