Frequency-dependent effects of quinidine on the relationship between action potential duration and refractoriness in the canine heart in situ.
To determine the normal relationship in vivo between action potential duration (APD) and effective refractory period (ERP) over a large range of steady-state cycle lengths (CLs) and to determine how a sodium channel-blocking agent, quinidine, affects this relationship, we developed a new contact electrode technique for simultaneous measurements of monophasic action potentials and refractoriness at a single site in the beating heart in situ. Recordings were made from left ventricular epicardium in open-chest dogs during steady-state pacing at CLs from 220 to 600 msec both before and after therapeutic intravenous administration of quinidine. During baseline both APD at 90% repolarization (APD90) and ERP were linearly correlated to CL with nearly identical slopes: y = 0.24x CL + 83.0 (r = 1.0; p less than .0001) for APD90 and y = 0.22x CL + 82.3 (r = 1.0; p less than .0001) for ERP. Expressed in percent repolarization, ERP coincided with a repolarization level of 79% to 83%, with no appreciable influence of CL on this relationship. Quinidine increased APD90 by a small but significant amount (8 to 12 msec), which was independent of CL. In contrast, the effect on ERP of quinidine exhibited marked frequency dependence (p less than .0002), producing progressively greater ERP increase at shorter CLs, as compared with both baseline ERP and concomitant APD90. The duration by which ERP exceeded APD90 reached 44 +/- 14 msec at a CL of 220 msec.(ABSTRACT TRUNCATED AT 250 WORDS)
Franz
M R
MR
Division of Cardiology, Stanford University School of Medicine, CA 94305.
Costard
A
A
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004285:Dogs; D004562:Electrocardiography / Q000295:instrumentation / Q000379:methods; D004566:Electrodes; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D011802:Quinidine / Q000494:pharmacology*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013997:Time Factors; D016276:Ventricular Function
D011802:Quinidine