Cocaine-induced supersensitivity and arrhythmogenesis

Hiroshi Inoue, Douglas P. Zipes

Research output: Contribution to journalArticle

48 Scopus citations


The mechanism of cocaine-related sudden death is unknown. To test whether cocaine potentiated changes in sinus cycle length, condaction 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 0.21) μg/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 cf 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 hy 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 < 0.03 versus without drugs). Induction of ventricular tachyarrhythmia during ansae subclaviae stimulation was not enhanced by cocaine in an additional 11 dogs with acute myocardial infarction. It is concluded that cocaine produces increased shortening of the ventricular effective refractory period in response to infused norepinephrine, but not in response to ansae subclaviae stimulation. Cocaine potentiates the development of ventricular tachycardia in dogs treated with norepinephrine infusion after acute myocardial infarction.

Original languageEnglish (US)
Pages (from-to)867-874
Number of pages8
JournalJournal of the American College of Cardiology
Issue number4
StatePublished - Apr 1988

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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