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: Moshe Swissa, Zhilin Qu, Toshihiko Ohara, Moon-Hyoung Lee, Shien-Fong Lin, Alan Garfinkel, Hrayr S Karagueuzian, James N Weiss, Peng-Sheng Chen
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 282 Issue 5 Pg. H1915-23 (May 2002) ISSN: 0363-6135 [Print] United States
• PMID: 11959659 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Arrhythmia Agents
• Bretylium Compounds
• diacetylmonoxime
• Verapamil
• Diacetyl
• bretylium
• Aconitine

Topics

• Aconitine (administration & dosage)
• Action Potentials
• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Bretylium Compounds (pharmacology)
• Computer Simulation
• Diacetyl (analogs & derivatives, pharmacology)
• Electrocardiography
• Female
• Male
• Swine
• Tachycardia, Ventricular (chemically induced, physiopathology)
• Ventricular Fibrillation (chemically induced, physiopathology)
• Verapamil (pharmacology)