The absence of insulin signaling in the heart induces changes in potassium channel expression and ventricular repolarization.

Diabetes mellitus increases the risk for cardiac dysfunction, heart failure, and sudden death. The wide array of neurohumoral changes associated with diabetes pose a challenge to understanding the roles of specific pathways that alter cardiac function. Here, we use a mouse model with cardiomyocyte-restricted deletion of insulin receptors (CIRKO, cardiac-specific insulin receptor knockout) to study the specific effects of impaired cardiac insulin signaling on ventricular repolarization, independent of the generalized metabolic derangements associated with diabetes.

Absence of glucose transporter 4 diminishes electrical activity of mouse hearts during hypoxia.

Insulin resistance, which characterizes type 2 diabetes, is associated with reduced translocation of glucose transporter 4 (GLUT4) to the plasma membrane following insulin stimulation, and diabetic patients with insulin resistance show a higher incidence of ischaemia, arrhythmias and sudden cardiac death. The aim of this study was to examine whether GLUT4 deficiency leads to more severe alterations in cardiac electrical activity during cardiac stress due to hypoxia. To fulfil this aim, we compared cardiac electrical activity from cardiac-selective GLUT4-ablated (G4H-/-) mouse hearts and corresponding control (CTL) littermates.

The maximal downstroke of epicardial potentials as an index of electrical activity in mouse hearts.

The maximal upstroke of transmembrane voltage (dV(m)/dt(max)) has been used as an indirect measure of sodium current I(Na) upon activation in cardiac myocytes. However, sodium influx generates not only the upstroke of V(m), but also the downstroke of the extracellular potentials V(e) including epicardial surface potentials V(es). The purpose of this study was to evaluate the magnitude of the maximal downstroke of V(es) (|dV(es)/dt (min)|) as a global index of electrical activation, based on the relationship of dV(m)/dt(max) to I(Na).

Experimental measures of ventricular activation and synchrony.

Background: A widened QRS complex as a primary indication for cardiac resynchronization therapy (CRT) for heart failure patients has been reported to be an inconsistent indicator for dyssynchronous ventricular activation. The purpose of this study was to conduct a detailed experimental investigation of total ventricular activation time (TVAT), determine how to measure it accurately, and compare it to the commonly used measure of QRS width. In addition, we investigated a measure of electrical synchrony and determined its relationship to the duration of ventricular activation.

Epicardial and intramural excitation during ventricular pacing: effect of myocardial structure.

Published studies show that ventricular pacing in canine hearts produces three distinct patterns of epicardial excitation: elliptical isochrones near an epicardial pacing site, with asymmetric bulges; areas with high propagation velocity, up to 2 or 3 m/s and numerous breakthrough sites; and lower velocity areas (<1 m/s), where excitation moves across the epicardial projection of the septum. With increasing pacing depth, the magnitude of epicardial potential maxima becomes asymmetric. The electrophysiological mechanisms that generate the distinct patterns have not been fully elucidated.