Effects of class I drugs on reentrant ventricular tachycardia in a canine model of myocardial infarction: on their antiarrhythmic and proarrhythmic mechanisms.
Mechanisms by which Class I drugs interrupt or facilitate reentrant ventricular tachycardia (VT) induced by programmed stimulation were analysed in dogs with 7-day-old myocardial infarction. Activation time and effective refractory period (ERP) were determined at 48 sites of survived epicardial layer within the infarction zone (IZ) and surrounding normal zone. Two mg/kg of lidocaine (L), propafenone (P) and flecainide (F) were administered intravenously. Induction of sustained VT was prevented by P in 7 of 10 cases, in 3 of 5 cases by F and in one of 8 cases by L (P vs L, p less than 0.01). Proarrhythmic effects were encountered in a case of P and 2 cases of F. Conduction velocity within the IZ was reduced by each drug to the same extent. The ERP within the IZ was prolonged by each drug, however, the mean extent of change differed significantly among the drugs (P 37% greater than F 26% greater than L 10%). In cases in which an antiarrhythmic effect was achieved, it was the result of abolition of the re-excitation at retrograde exit site of reentry circuit, which was considered to be due to prolongation of refractoriness at the site. These results suggest that prolongation of local refractoriness within the IZ is the major antiarrhythmic mechanism. The proarrhythmic effect was accompanied by an increased dispersion of local ERP as well as by a marked reduction of conduction velocity within the IZ.
Miyazaki
T
T
Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Ogawa
S
S
Sakai
T
T
Hosokawa
M
M
Sakurai
K
K
Nakamura
Y
Y
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D008297:Male; D009203:Myocardial Infarction; D013610:Tachycardia / Q000503:physiopathology*
D000889:Anti-Arrhythmia Agents