Cocaine-induced supersensitivity and arrhythmogenesis.
The mechanism of cocaine-related sudden death is unknown. To test whether cocaine potentiated changes in sinus cycle length, conduction in the atrioventricular node (AH interval) and ventricular effective refractory period induced by infused norepinephrine and ansae subclaviae stimulation, the dose-response curves of sinus cycle length, AH interval and ventricular effective refractory period to infused norepinephrine (0.01 to 0.20 micrograms/kg body weight per min) and the frequency-response curves to ansae subclaviae stimulation (1 to 4 Hz, 2 to 3 mA, 4 ms pulses) were determined before and after intravenous injection of cocaine (5 mg/kg) in 15 anesthetized open chest dogs. Cocaine potentiated shortening of sinus cycle length, AH interval and ventricular effective refractory period induced by norepinephrine infusion and shifted dose-response curves of these variables to the left in eight dogs (supersensitivity). Cocaine did not affect frequency-response curves of sinus cycle length and AH interval to ansae subclaviae stimulation. Ansae subclaviae stimulation shortened the ventricular effective refractory period more after cocaine injection, but frequency-response curves were not shifted to the left in seven dogs (no supersensitivity). Cocaine did not enhance electrical induction of ventricular tachyarrhythmias in 15 dogs without acute myocardial infarction. Acute myocardial infarction was produced by coronary artery ligation in another group of 21 dogs. Of 10 dogs with acute myocardial infarction, spontaneous or electrically induced ventricular tachycardia developed in 1 dog without drugs, in 3 dogs given norepinephrine and in 7 dogs given norepinephrine and cocaine (p less than 0.03 versus without drugs).(ABSTRACT TRUNCATED AT 250 WORDS)
Inoue
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Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis 46202.
Zipes
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DP
D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects*; D003042:Cocaine / Q000009:adverse effects*; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000503:physiopathology*; D009431:Neural Conduction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000503:physiopathology; D013610:Tachycardia / Q000139:chemically induced* / Q000209:etiology / Q000503:physiopathology
D003042:Cocaine; D009638:Norepinephrine