Jiashin Wu

The QT syndromes: long and short

This Seminar presents the most recent information about the congenital long and short QT syndromes, emphasising the varied genotype-phenotype association in the ten different long QT syndromes and the five different short QT syndromes. Although uncommon, these syndromes serve as a Rosetta stone for the understanding of inherited ion-channel disorders leading to life-threatening cardiac arrhythmias. Ionic abnormal changes mainly affecting K(+), Na(+), or Ca(2+) currents, which either prolong or shorten ventricular repolarisation, can create a substrate of electrophysiological heterogeneity that predisposes to the development of ventricular tachyarrhythmias and sudden death. The understanding of the genetic basis of the syndromes is hoped to lead to genetic therapy that can restore repolarisation. Presently, symptomatic individuals are generally best treated with an implantable cardioverter defibrillator. Clinicians should be aware of these syndromes and realise that drugs, ischaemia, exercise, and emotions can precipitate sudden death in susceptible individuals.

Cytochalasin D as excitation-contraction uncoupler for optically mapping action potentials in wedges of ventricular myocardium.

Myocardium Immobilization for Repolarization Mapping. Introduction: Cytochalasin D In tissue bath superfusate inhihits the contraction of isolated thin trabeculae from canine right ventricle without affecting the intracellular action potential recorded with glass microelectrode. The purpose of this study was to test whether cytochalasin D could also be used to immobilize perfused wedges of ventricular muscle without affecting the action potential duration or propagation, and also to determine the optimal concentration and time duration of drug in the perfusate.

Differential effects of cytochalasin D and 2,3 butanedione monoxime on isometric twitch force and transmembrane action potential in isolated ventricular muscle: implications for optical measurements of cardiac repolarization.

Cytochalasin D Induced Cardiac Contraction Failure. Introduction: 2,3‐Butanedione monoxime (BDM) has been widely used to inhibit contraction during optical recordings of cardiac membrane voltage changes, even though it markedly abbreviates cardiac action potentials.

Effects of spatial segmentation in the continuous model of excitation propagation in cardiac muscle.

Spatial Segmentation in the Simulation of Propagation. Introduction: Spatial segmentation is essential for the numerical simulation of excitation propagation in cardiac muscle.

Mechanisms of Initiation of Ventricular Tachyarrhythmias

The mechanisms responsible for ventricular tachyarrhythmia (VT) initiation have been studied extensively since the beginning of the last century. Multiple approaches including clinical observations; experiments in vivo, in vitro, and at cellular and genetic levels; theoretical analysis; and numeric simulations have been used. Most VTs are initiated by spontaneous discharge(s) at one or several sites in the ventricle, which can contribute to, or precipitate, reentry that then maintains the VT. Although most VTs occur in abnormal hearts such as in patients with coronary artery diseases, cardiomyopathy, abnormal ionic currents, or other problems, VT can also be functional, occurring in seemingly normal hearts when the conditions for its initiation are met. Because of the possible outcome of sudden cardiac death and the increasingly aging population in the industrialized countries, managing VT is a significant and important clinical task. Understanding the mechanisms of its initiation is one of the key steps in developing clinical strategies to prevent and treat VT. However, the mechanisms of VT initiation are still not fully understood and are the topic for a brief overview in this chapter.

Acute ischemia of canine interventricular septum produces asymmetric suppression of conduction.

BACKGROUND Acute ischemia depresses tissue excitability more rapidly in the epicardium than in the endocardium of the canine left ventricular (LV) free wall. However, the effects of acute ischemia on conduction in the interventricular septum (IVS), which is composed of right ventricular (RV) and LV endocardium and midmyocardium without epicardium, are less known. OBJECTIVE The purpose of this study was to evaluate the hypothesis that the IVS exhibits transseptal differences in local tissue response to acute ischemia. METHODS Isolated canine IVS preparations were perfused through the septal branch of the anterior descending coronary artery, and conduction on the cut-exposed transseptal surfaces was optically mapped before and after two sequential episodes of 8 minutes of global ischemia (separated by >60 minutes of reperfusion). The preparations were paced alternately between the RV endocardium and LV endocardium at cycle lengths of 250, 300, and 1,500 ms. RESULTS Prior to ischemia, transseptal conduction was radial and symmetric during either RV endocardial or LV endocardial pacing at all cycle lengths. Eight minutes of ischemia depressed conduction velocity more in the RV half than in the LV half of the IVS and caused local conduction block in the sub-RV endocardium, especially during rapid pacing. The K(ATP) channel blocker glibenclamide (10 micromol/L) prevented development of this transseptal asymmetry and conduction block during ischemia. CONCLUSION Acute global ischemia increased transseptal heterogeneity and induced sub-RV endocardial block of conduction via activation of the ATP-sensitive potassium current. Such changes could contribute to initiation of arrhythmia in patients with septal infarction.

1130-221 Prior ischemia enhances arrhythmogenicity in isolated canine ventricular wedge model of long QT 3

OBJECTIVE Ventricular tachyarrhythmias (VTs) occur frequently in patients having long QT syndrome (LQTS) or after acute myocardial ischemia. However, the synergistic effects of ischemia and LQTS on arrhythmia development are unclear. We evaluated the contribution of a prior episode of ischemia on the arrhythmogenicity of the LQTS. METHODS Using a 256-channel optical mapping system, we mapped action potentials on the cut-exposed transmural surfaces of perfused and preconditioned muscle wedges isolated from canine left ventricular walls and recorded their transmural electrocardiogram (ECG). RESULTS We observed that 40 min of global ischemia followed by 60 min of reperfusion, at which time action potential duration (APD) and conduction velocity had recovered, significantly enhanced the APD prolongation produced by 20 nmol/l anemone toxin II (ATX-II). Wedges after the above ischemia, reperfusion, and ATX-II procedures had 100% (8/8) occurrences of early afterdepolarizations (EADs) and 87.5% (7/8) occurrences of spontaneous VTs and reentry. We observed epicardial, midmyocardial, and endocardial occurrences of EADs in one, seven, and four wedges, respectively. Focal EADs and reentry were responsible for 73% and 18% of the repetitive activations in the VTs. In contrast, neither EADs nor VTs occurred in eight control wedges following identical procedures except without ischemia, and VT occurred in 20% wedges (2/10) after ischemia and reperfusion but before ATX-II. CONCLUSION A prior episode of acute ischemia, even after apparent electrophysiologic recovery, enhances the arrhythmogenicity of LQTS induced by ATX-II through the development of EADs and reentry.