title: Effects of pacing on triggered activity induced by early afterdepolarizations.
abstract: Early afterdepolarizations (EADs) are depolarizing potentials that occur during phase 2 or phase 3 of repolarization. They can induce triggered activity and have been proposed as a cause for arrhythmias in the heart in situ. To determine the response of EADs and triggered activity to interventions analogous to those used in the clinic for identifying arrhythmogenic mechanisms, we used a pacing protocol to study the response of EADs to sustained drive and extrastimuli. Cesium chloride (5 to 20 mM), which induces triggered arrhythmias in the intact dog, was used to induce EADs in isolated canine Purkinje fibers, and these were studied by microelectrode techniques. Cesium prolonged action potential duration and induced two types of EADs. At a potassium concentration of 4 mM, EADs occurred at membrane potentials of -3 to -30 mV. They were initiated 240 to 680 msec after the action potential upstroke and were 2 to 30 mV in amplitude. Their amplitude increased as drive cycle length increased, but their coupling interval to the action potential did not change with drive cycle length. These EADs did not induce triggered action potentials. At a potassium concentration of 2 mM, EADs usually occurred at higher membrane potentials (-50 to -70 mV) and longer coupling intervals (470 to 1360 msec) and were manifested as a delay of phase 3 repolarization. These EADs induced triggered action potentials. When the triggered rhythms became sustained, premature stimuli either reset or terminated them, depending on the maximum diastolic potential. Termination occurred more frequently as the maximum diastolic potential increased. The extent of overdrive suppression induced by pacing for 15 sec to 3 min also increased as the maximum diastolic potential increased. In summary, cesium induced EADs at low or high membrane potentials. The former did not induce triggered activity, but the latter did. The triggered rhythms that occurred were similar to abnormal automatic mechanisms in their response to overdrive pacing and extrastimuli.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D002304:Cardiac Pacing, Artificial; D002586:Cesium / Q000494:pharmacology*; D004285:Dogs; D004562:Electrocardiography; D006329:Heart Conduction System / Q000503:physiopathology*; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D011690:Purkinje Fibers / Q000503:physiopathology*
chemical_list: D002586:Cesium; D011188:Potassium