title: Epinephrine facilitates cardiac fibrillation by shortening action potential refractoriness.
abstract: Epinephrine released during ventricular tachycardia (VT) or early fibrillation (VF) appears to be instrumental in stabilizing fibrillation. However, mechanisms remain unclear. Effects of epinephrine on refractory period at normal sinus rates depend on basic cycle length, but effects at short cycle lengths, typical of VT/VF, are unknown. Therefore, the goal of this study was to determine whether epinephrine shortens action potential duration and refractoriness at these short cycle lengths. To simulate early VT/VF, myocardial cell aggregates (n = 35) were paced using field stimulation (5 ms rectangular waveform) at cycle lengths of 200, 180, 160 and 140 ms, which occur during in situ fibrillation: normal sinus rhythm was simulated by pacing at 600 and 400 ms intervals. Action potentials and excitation threshold were recorded with intracellular microelectrodes under control conditions, with 0.9 microM/l epinephrine, and with 0.9 microM/l epinephrine and 0.5 microM/l propranolol. At short cycle lengths, epinephrine significantly shortened action potential duration and refractoriness compared to control. At a cycle length of 160 ms, action potential duration was reduced by 14 ms at 60% repolarization (P < 0.0002) and stimulation threshold by 18% (P < 0.02). Epinephrine also allowed pacing at a cycle length of 140 ms, not achievable under control conditions. Because epinephrine decreases action potential duration at short cycle length in situ, re-entry wavefronts are less likely to encounter refractory tissue: fibrillation is more likely to occur and to remain stabilised. Reduction in action potential duration and excitation threshold were reversed by propranolol, suggesting that epinephrine effects are produced by beta-stimulation.
authors.affiliation: Cardiac Research Laboratory, Department of Veterans Affairs Medical Center, Washington, DC 20422, USA.
authors.forename: O H
authors.initials: OH
authors.lastname: Tovar
authors.forename: J L
authors.initials: JL
authors.lastname: Jones
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002642:Chick Embryo; D004837:Epinephrine / Q000494:pharmacology*; D066298:In Vitro Techniques; D012032:Refractory Period, Electrophysiological / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000889:Anti-Arrhythmia Agents; D004837:Epinephrine