title: Action potential duration restitution and ventricular fibrillation due to rapid focal excitation.
abstract: The focal source hypothesis of ventricular fibrillation (VF) posits that rapid activation from a focal source, rather than action potential duration (APD) restitution properties, is responsible for the maintenance of VF. We injected aconitine (100 microg) into normal isolated perfused swine right ventricles (RVs) stained with 4-[beta-[2-(di-n-butylamino)-6-naphthyl]vinyl]pyridinium (di-4-ANEPPS) for optical mapping studies. Within 97 +/- 163 s, aconitine induced ventricular tachycardia (VT) with a mean cycle length 268 +/- 37 ms, which accelerated before converting to VF. Drugs that flatten the APD restitution slope, including diacetyl monoxime (10-20 mM, n = 6), bretylium (10-20 microg/ml, n = 3), and verapamil (2-4 microg/ml, n = 3), reversibly converted VF to VT in all cases. In two RVs, VF persisted despite of the excision of the aconitine site. Simulations in two-dimensional cardiac tissue showed that once VF was initiated, it remained sustained even after the "aconitine" site was eliminated. In this model of focal source VF, the VT-to-VF transition occurred due to a wave break outside the aconitine site, and drugs that flattened the APD restitution slope converted VF to VT despite continuous activation from aconitine site.
authors.affiliation: Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
authors.forename: Moshe
authors.initials: M
authors.lastname: Swissa
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Qu
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ohara
authors.forename: Moon-Hyoung
authors.initials: MH
authors.lastname: Lee
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
authors.forename: Alan
authors.initials: A
authors.lastname: Garfinkel
authors.forename: Hrayr S
authors.initials: HS
authors.lastname: Karagueuzian
authors.forename: James N
authors.initials: JN
authors.lastname: Weiss
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
mesh_terms: D000157:Aconitine / Q000008:administration & dosage; D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001949:Bretylium Compounds / Q000494:pharmacology; D003198:Computer Simulation; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D004562:Electrocardiography; D005260:Female; D008297:Male; D013552:Swine; D017180:Tachycardia, Ventricular / Q000139:chemically induced* / Q000503:physiopathology*; D014693:Ventricular Fibrillation / Q000139:chemically induced* / Q000503:physiopathology*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D001949:Bretylium Compounds; C004717:diacetylmonoxime; D014700:Verapamil; D003931:Diacetyl; C045166:bretylium; D000157:Aconitine