A mathematical model of phase 2 reentry: role of L-type Ca current.
Phase 2 reentry (P2R) is known to be one of the mechanisms of malignant ventricular arrhythmias, especially those associated with Brugada syndrome. However, little is known about the underlying mechanism for P2R. Our aim in this study was to simulate P2R in a mathematical model to enable us to understand its mechanism and identify a potential therapeutic target. A mathematical model of the L-type Ca current was composed according to whole cell current data from guinea pig ventricular myocytes recorded at 37 degrees C. Our mathematical model was incorporated into the modified Luo-Rudy phase 2 model. We set a dispersion in transient outward current (I(to)) density within the theoretical fiber, composed of 80 serially arranged epicardial cells with gap junctions and then observed the P2R. The dispersion in I(to) density within an only 0.8-cm epicardial theoretical fiber generated P2R with our Ca channel but not with the original model. When the P2R developed in the theoretical fiber, the calculated extracellular field potential showed coved-type ST segment elevation. We succeeded in generating P2R in our model for the first time. The local epicardial P2R may contribute the genesis of coved-type ST segment elevation in the Brugada syndrome.
Miyoshi
Shunichiro
S
Department of Physiology, Keio University School of Medicine, and Pharmacia Laboratory, Tokyo, 160-8582 Japan. smiyoshi@cpnet.med.keio.ac.jp
Mitamura
Hideo
H
Fujikura
Kana
K
Fukuda
Yukiko
Y
Tanimoto
Kojiro
K
Hagiwara
Yoko
Y
Ita
Makoto
M
Ogawa
Satoshi
S
D000200:Action Potentials; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D003198:Computer Simulation; D004553:Electric Conductivity; D004562:Electrocardiography; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D008433:Mathematics; D008564:Membrane Potentials; D008954:Models, Biological; D018408:Patch-Clamp Techniques; D010496:Pericardium / Q000502:physiology; D016276:Ventricular Function
D020746:Calcium Channels, L-Type