Onset dynamics of reentrant tachycardia and rate-dependent conduction changes in canine ventricular muscle: effects of Na+ and Ca2+ channel blockade.
To show that cycle-length (CL) prolongation occurring at the onset of reentrant tachycardias may be associated with an increase in conduction time (CT), and to investigate the involvement of Na+ and Ca2+ channel activity, reentrant activity was induced by programmed stimulation in thin ventricular muscle slices with a central cryothermal lesion, as documented with 7 to 12 bipolar recordings. We studied the course of the CL measured in successive tachycardia beats, as well as the course of conduction times after abrupt transition from a pacing CL of 1,000 to 400 ms (pacing paradigm). The majority of the tachycardias displayed a dynamic behavior in which CL increased progressively, with an exponential rate constant of 37 +/- 35 beats (mean +/- SD), stabilizing at 325 +/- 67 ms after a total increase of 17 +/- 17 ms. In the pacing paradigm, CT was prolonged from 68 +/- 21 ms to 79 +/- 24 ms according to a biphasic course consisting of an abrupt increase in the first response to 400 ms, followed up by an exponential increase, stabilizing with a rate constant of 18 +/- 23 beats. Lidocaine 5 x 10(-5) mol/L induced an increase in steady-state CT, which was not further modified by adding verapamil 10(-5) mol/L. However, verapamil prolonged the rate constant of the exponential course by 60 +/- 40 beats. Thus, the onset dynamics of reentrant tachycardias share common features with the dynamic behavior of CT in the pacing paradigm, in which both Na+ channel activity and Ca2+-modulated cellular coupling appear to be involved.
Lemarbre
F
F
Département de Pharmacologie, Faculté de Médecine, Université de Montréal, Québec, Canada.
Vinet
A
A
Vermeulen
M
M
Cardinal
R
R
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D003627:Data Interpretation, Statistical; D004285:Dogs; D004562:Electrocardiography / Q000379:methods*; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects*; D017180:Tachycardia, Ventricular / Q000503:physiopathology*; D014700:Verapamil / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D015222:Sodium Channels; D008012:Lidocaine; D014700:Verapamil