Mechanisms underlying the antiarrhythmic and arrhythmogenic actions of quinidine in a Purkinje fiber-ischemic gap preparation of reflected reentry.
The effects of therapeutic levels of quinidine were studied in an ischemic gap preparation of reflected reentry. The preparation consisted of a Purkinje fiber mounted in a three-compartment chamber. A narrow central compartment was perfused with a solution prepared to mimic the extracellular milieu at a site of ischemia. Quinidine in concentrations that exert little effect on normal Purkinje tissue, 1 to 2 micrograms/ml, greatly impaired conduction and markedly prolonged refractoriness across the ischemic gap. The drug effected these changes by (1) extending the inexcitable zone within the depressed region, (2) decreasing the amplitude of the input signal entering this zone, and (3) decreasing the excitability of the tissue beyond the depressed zone (evaluated by current clamp techniques). These actions of the drug produced both antiarrhythmic and proarrhythmic effects. When the initial level of conduction impairment was high, quinidine totally suppressed reflected reentry at all frequencies by precipitating complete anterograde conduction block. At intermediate levels of block, the drug generally caused a prominent shift of the frequency dependence of reentrant activity to lower stimulation rates. Finally, when conduction was relatively less impaired, quinidine created the conditions for reflected reentry to occur. Our results suggest that the heart rate dependence of reentrant arrhythmias might be of prognostic value in the administration of antiarrhythmic drugs.
X T
XT
Shen
C
C
Antzelevitch
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D003327:Coronary Disease / Q000503:physiopathology; D004285:Dogs; D004562:Electrocardiography; D004594:Electrophysiology; D006329:Heart Conduction System / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D008839:Microelectrodes; D011690:Purkinje Fibers / Q000503:physiopathology*; D011802:Quinidine / Q000494:pharmacology*; D013997:Time Factors
D011802:Quinidine