Effects of quinidine on repolarization in canine epicardium, midmyocardium, and endocardium: II. In vivo study.
BACKGROUND
In the companion article, we report a significant difference in quinidine effects on the action potential duration between surface (epicardial and endocardial) cells and midmyocardial cells (M cells) of canine left ventricle in vitro. This article considers two questions raised by the previous study: (1) Are the complex quinidine effects in vitro reflected in its actions on the heart in situ? (2) What are the cellular determinants of quinidine effects on QT interval in ECG?


RESULTS
We used plunge and surface electrodes to measure activation-recovery intervals (ARIs) of bipolar electrograms obtained from epicardium, endocardium, and midmyocardium (3, 5, and 9 mm from epicardium) of canine left ventricle in conditions of AV block and right ventricular pacing. Quinidine was infused continuously; its plasma level increased from 1.6+/-0.1 microg/mL at 30 minutes to 7.6+/-0.7 microg/mL at 180 minutes. At cycle lengths (CLs) from 300 to 1500 ms, there was no ARI gradient across the ventricular wall before and during quinidine infusion. At a CL of 300 ms, therapeutic concentrations of quinidine prolonged ARIs and QT intervals. At a CL of 1500 ms, ARIs were significantly prolonged at low quinidine concentrations. With an increase of quinidine concentration, this effect subsided and disappeared.


CONCLUSIONS
In situ, quinidine-induced prolongation of repolarization is uniform in all myocardial layers and follows the pattern observed in M cells in vitro. The ability of quinidine in therapeutic concentrations to prolong repolarization at rapid heart rates can contribute to its antiarrhythmic efficacy.
Anyukhovsky
E P
EP
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Sosunov
E A
EA
Feinmark
S J
SJ
Rosen
M R
MR
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D004699:Endocardium / Q000187:drug effects*; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D008297:Male; D010496:Pericardium / Q000187:drug effects*; D011802:Quinidine / Q000494:pharmacology*; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D011802:Quinidine