title: Intracoronary versus intravenous effects of cocaine on coronary flow and ventricular function.
abstract: BACKGROUND
  Cocaine use has been associated with cardiomyopathy and ischemic coronary syndromes. However, the pathophysiological mechanisms responsible for these syndromes are not clear and have been suggested to involve direct effects of cocaine on myocyte contractility and coronary resistance as well as indirect effects via altered autonomic tone, secondary mediators, and myocardial metabolism. We sought to distinguish direct from indirect effects of cocaine on ventricular function and coronary resistance by comparison of the administration of intracoronary cocaine (0.12 to 0.36 mg/min constant infusion) with intravenous cocaine (5 mg/kg bolus infusion) in an in vivo anesthetized pig preparation.
  
  
  RESULTS
  To control for changes in coronary resistance secondary to autoregulation and myocardial metabolism, the left anterior descending coronary artery was perfused at constant coronary pressure and the interventricular vein was cannulated for coronary venous oxygen saturation measurement. Coronary blood flow, regional percent segment shortening, myocardial oxygen consumption, and serum cocaine concentrations were measured. Intracoronary cocaine produced a dose-dependent decrease in percent segment shortening in the absence of significant changes in coronary flow or systemic hemodynamics. In contrast, intravenous cocaine had mild biphasic effects on coronary resistance with an initial brief vasodilation (30.0 +/- 5% increase in flow from control) followed by more prolonged vasoconstriction (17.0 +/- 3.3% decrease in flow from control), which were independent of autoregulation or myocardial metabolism. In addition, intravenous cocaine caused an early 48% decrease in percent segment shortening, at which time the measured cocaine concentration was 20.1 micrograms/mL blood. This was comparable to the intracoronary cocaine concentration of 17.1 micrograms/mL blood, which produced a similar 48% decrease in percent segment shortening.
  
  
  CONCLUSIONS
  We conclude that the effects of acute cocaine exposure on ventricular function are predominantly direct but of brief duration and therefore probably not clinically relevant. The effects of cocaine on coronary tone are predominantly indirect and biphasic, with early vasodilation followed by mild and more prolonged vasoconstriction. In the absence of coronary stenosis or ventricular hypertrophy, this small amount of vasoconstriction is unlikely to cause ischemia.
authors.affiliation: Department of Medicine, University of California, San Diego.
authors.forename: H J
authors.initials: HJ
authors.lastname: Zimring
authors.forename: R L
authors.initials: RL
authors.lastname: Fitzgerald
authors.forename: R L
authors.initials: RL
authors.lastname: Engler
authors.forename: B R
authors.initials: BR
authors.lastname: Ito
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage* / Q000009:adverse effects*; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects; D005260:Female; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D003042:Cocaine