Spatiotemporal dynamics of reentrant ventricular tachycardias in canine myocardial infarction: pharmacological modulation.
During the transition from a slow to rapid depolarization rhythm, rate-dependent sodium channel blockade develops progressively and increases from beat to beat under procainamide but more abruptly under lidocaine. We investigated the consequences of such differences on the dynamic course and stability of reentrant tachycardias at their onset. Procainamide and lidocaine were infused to equipotent plasma concentrations in canines with three-day-old myocardial infarction. We measured the activation times (ms) and maximum slopes of negative deflections in activation complexes (absolute value: /-dV/dt(max)/ in mV/ms) in 191 unipolar electrograms recorded from ischemically damaged subepicardial muscle during programmed stimulation inducing reentrant tachycardias. Procainamide caused a greater reduction in /-dV/dt(max)/ than did lidocaine in the responses to basic stimulation, and it favored the occurrence of cycle length prolongation at tachycardia onset as the /-dV/dt(max)/ decreased progressively in successive beats. This resulted in conduction block and tachycardia termination in three of eight preparations. In contrast, lidocaine caused a greater depression in /-dV/dt(max)/ in response to closely coupled extrastimuli, but /-dV/dt(max)/ remained constant or even improved thereafter, and none of the tachycardias terminated spontaneously under lidocaine (n = 9). However, the reentrant circuits remained spatially unstable, and lidocaine favored the occurrence of cycle length dynamics displaying constant or decreasing trends. This study supports the notion that cycle length dynamics at tachycardia onset are determined by the properties of the reentrant substrate and their pharmacological modulation.
Hélie
François
F
The Research Center, Hôpital du Sacré-Coeur de Montréal, 5400 Gouin Boulevard West, Montréal, QC H4J 1C5, Canada.
Vinet
Alain
A
Cardinal
René
R
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000503:physiopathology*; D011342:Procainamide / Q000494:pharmacology; D017180:Tachycardia, Ventricular / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D008012:Lidocaine; D011342:Procainamide