EXPERIMENTAL-MODELS OF TORSADE-DE-POINTES

Torsade de pointes is a potentially life threatening form of polymorph ic ventricular tachycardia typically seen in the setting of congenital and acquired abnormal QT-prolongation. Numerous in vitro studies have investigated basic ionic mechanisms underlying delayed repolarization . The role of different ion channels and the induction of early afterd epolarizations have been studied in various cardiac cells including M cells. In addition, isolated heart models with and without electrical stimulation and/or the use of drugs which prolong repolarization have been developed in recent years. Some of these models have simulated co nditions likely to exist in the clinical setting of torsade de pointes , such as bradycardia and hypokalemia. In in vivo canine and rabbit mo dels, torsade-like polymorphic ventricular tachyarrhythmias have been induced by the administration of different agents such as cesium, neur otoxins, e.g., anthopleurin or various class III drugs under condition s designed to mimic the clinical situation. In the context of recent a dvances in the molecular genetics of long QT syndrome, those models wh ich have used sodium or potassium channel blockers have gained particu lar interest. Based on all experimental studies it seems probable that the first beats of torsade occur due to early afterdepolarizations an d triggered activity. The development of subsequent beats is less clea r. Reentry based on inhomogeneity of refractoriness has been suggested as the underlying mechanism. (C) 1998 Elsevier Science B.V. AU rights reserved.