Frequency-Dependent Effects of Several Class I Antiarrhythmic Drugs on &OV0312;max of Action Potential Upstroke in Canine Cardiac Purkinje Fibers

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Abstract
JOURNAL/jcph/04.02/00005344-198505000-00011/ENTITY_OV0312/v/2017-07-28T024952Z/r/image-pngmax of the action potential upstroke in canine cardiac Purkinje fibers was studied in the presence of seven class I antiarrhythmic drugs—lidocaine (4 μg/ml), mexiletine (4 μg/ml), propranolol (0.9 μg/ml), procainamide (30 μg/ml), quinidine (5 μg/ml), flecainide (4 μg/ml), and disopyramide (3.1 μg/ml)—at constant cycle lengths (CCL) and after abrupt changes in cycle length (ACCL). The time constant of JOURNAL/jcph/04.02/00005344-198505000-00011/ENTITY_OV0312/v/2017-07-28T024952Z/r/image-pngmax recovery after ACCL at a basic cycle length of 500 ms was 0.09 ± 0.01 s for lidocaine, 0.18 ± 0.03 s for mexiletine, 1.35 ± 0.20 s for propranolol, 4.4 ± 0.8 s for procainamide, 8.3 ± 1.2 s for quinidine, 11.0 ± 0.9 s for flecainide, and 37.9 ± 9.4 s for disopyramide. These values were similar to those reported by others in guinea pig papillary muscle, and, with the exception of flecainide, conformed to the scheme proposed by Courtney (J Mol Cell Cardiol 1980;12:1273–86) based on the molecular weight and lipid solubility hypothesis. Each drug altered the JOURNAL/jcph/04.02/00005344-198505000-00011/ENTITY_OV0312/v/2017-07-28T024952Z/r/image-pngmax differently at CCL from after ACCL at the same diastolic intervals. The magnitude of these differences and the range of diastolic intervals at which they were present varied among different drugs. These observations explain differences in the drug effects on the JOURNAL/jcph/04.02/00005344-198505000-00011/ENTITY_OV0312/v/2017-07-28T024952Z/r/image-pngmax of the regularly and prematurely occurring depolarizations. In the presence of lidocaine and mexiletine, the recovery kinetics of JOURNAL/jcph/04.02/00005344-198505000-00011/ENTITY_OV0312/v/2017-07-28T024952Z/r/image-pngmax were not altered by CCL within the 300–1,500-ms range, and the magnitude of JOURNAL/jcph/04.02/00005344-198505000-00011/ENTITY_OV0312/v/2017-07-28T024952Z/r/image-pngmax depression was not influenced by action potential duration within the 200–270-ms range.