Action potential duration restitution and ventricular fibrillation due to rapid focal excitation.
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.
Swissa
Moshe
M
Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Qu
Zhilin
Z
Ohara
Toshihiko
T
Lee
Moon-Hyoung
MH
Lin
Shien-Fong
SF
Garfinkel
Alan
A
Karagueuzian
Hrayr S
HS
Weiss
James N
JN
Chen
Peng-Sheng
PS
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
D000889:Anti-Arrhythmia Agents; D001949:Bretylium Compounds; C004717:diacetylmonoxime; D014700:Verapamil; D003931:Diacetyl; C045166:bretylium; D000157:Aconitine