Effects of procainamide and sotalol on restitution properties, dispersion of refractoriness, and ventricular fibrillation activation patterns in pigs.
BACKGROUND
Interest in combining antiarrhythmic drugs has been prompted by the lack of efficacy of monotherapies and the toxicity resulting from high doses of individual agents.


OBJECTIVE
We tested the hypothesis that procainamide and sotalol combined have greater beneficial effects on restitution, on the dispersion of refractoriness, and on decreasing the complexity of ventricular fibrillation (VF) than either drug alone.


METHODS
Six open-chest pigs received intravenous procainamide (15 mg/kg load and 50 microg/kg/min maintenance) followed by sotalol (1.5 mg/kg). Another six pigs received sotalol first and procainamide second. Before drugs and after each drug, 20-second episodes of electrically induced VF were recorded from a 21 x 24 unipolar electrode plaque (2 mm spacing) sutured on the lateral posterior left ventricular epicardium. Restitution properties and dispersion of refractoriness were estimated from activation recovery intervals during pacing.


RESULTS
The combination of the two drugs reduced the maximum slope of the restitution curve and during VF reduced the number of wavefronts, the activation rate, the percentage of wavefront families exhibiting reentry, and the conduction velocity more than either drug alone. In addition, in the group that received sotalol first, both drugs together reduced the SD and the coefficient of variation of the spatial dispersion of refractoriness compared with baseline.


CONCLUSIONS
Procainamide and sotalol combined have greater beneficial effects on restitution properties, dispersion of refractoriness, and the complexity of VF than either drug alone compared with baseline.
Jin
Qi
Q
Department of Cardiology, Shanghai Rui Jin Hospital, Jiaotong University School of Medicine, Shanghai, PR China.
Chen
Xiaozhong
X
Smith
William M
WM
Ideker
Raymond E
RE
Huang
Jian
J
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D004562:Electrocardiography / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects*; D007273:Injections, Intramuscular; D011342:Procainamide / Q000008:administration & dosage*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013015:Sotalol / Q000008:administration & dosage*; D013552:Swine; D016896:Treatment Outcome; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology*
D000889:Anti-Arrhythmia Agents; D013015:Sotalol; D011342:Procainamide