cytochalasin-d and Myocardial-Ischemia

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.. 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).. 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.. 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.

Topics: Action Potentials; Animals; Cardiac Pacing, Artificial; Culture Techniques; Cytochalasin D; Dogs; Heart; Heart Ventricles; Long QT Syndrome; Models, Animal; Myocardial Ischemia

Extracellular oxygen radicals produced by H9c2 rat heart cells in monolayer cultures during ischemia and subsequent reoxygenation were monitored using the luminol-horseradish peroxidase-enhanced chemiluminescence technique. As expected, the photon count diminishes during ischemia but again rapidly attains normal values following reoxygenation. In the presence of superoxide dismutase, this photon emission is repressed, as is also the case in the presence of diphenylene iodonium, a specific inhibitor of NADPH-oxidase activity. Thus, the conclusion seems justified that H9c2 rat heart cells in monolayer cultures produce superoxide radicals extracellularly due to an NADPH oxidase-like action. In order to characterize this extracellular superoxide-generating system, we determined its sensitivity to increased temperatures, inhibition of protein synthesis and perturbations of cytoskeletal structures. Heat shocks result in a delayed inactivation of the NADPH oxidase activity followed by recovery, the kinetics of which depend on the imposed heat shock temperature. This inactivation is independent of protein synthesis and actin cytoskeletal structures, but the recovery of the enzyme's activity is dependent on these entities.

Topics: Animals; Cell Line; Cycloheximide; Cytochalasin D; Heat-Shock Response; Myocardial Ischemia; Myocardium; NADPH Oxidases; Nucleic Acid Synthesis Inhibitors; Oxygen; Protein Synthesis Inhibitors; Rats; Superoxides