Electrical heterogeneity and arrhythmogenesis: importance of conduction velocity dispersion.
An experimental model of conduction velocity (CV) and refractory period dispersion was established to determine which variable is a determinant of myocardial vulnerability. Anesthetized swine were instrumented with a left anterior descending coronary artery catheter for regional infusion of lidocaine (n = 6), low-dose d-sotalol (n = 4), high-dose d-sotalol (n = 6), or saline (n = 6), to create dispersion in CV (lidocaine), refractoriness (d-sotalol), or neither (saline). Ventricular fibrillation thresholds (VFTs) and refractory periods were determined at five sites (one drug perfused, four non-drug perfused). CV was determined in one drug-perfused area (left ventricular epicardial apex) and one non-drug perfused area (right ventricular epicardial base). Lidocaine and low- and high-dose d-sotalol increased VFT when stimuli were delivered in the drug-perfused area. However, lidocaine decreased VFT when stimuli were delivered at non-drug perfused areas by an average of 52%. Neither d-sotalol dose affected VFT when stimuli were delivered in non-drug perfused areas. Lidocaine increased CV dispersion by 18-26 cm/s but did not alter refractoriness. Both d-sotalol doses increased dispersion in refractoriness by 15-27 ms but did not alter CV. Saline did not affect either variable. Regional lidocaine had profibrillatory effects when stimuli were delivered in non-drug perfused areas, whereas regional d-sotalol did not. Hence, CV dispersion is a more likely determinant of myocardial vulnerability than refractoriness.
Sims
J Jason
JJ
University of Georgia College of Pharmacy, Medical College of Georgia, Augusta, USA. jjsims@pharmacy.wisc.edu
Miller
Allison W
AW
Ujhelyi
Michael R
MR
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000503:physiopathology*; D003331:Coronary Vessels; D004195:Disease Models, Animal; D004562:Electrocardiography; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D007260:Infusion Pumps; D008012:Lidocaine / Q000494:pharmacology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects / Q000502:physiology; D013015:Sotalol / Q000494:pharmacology; D013552:Swine; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D008012:Lidocaine; D013015:Sotalol