Cocaine-induced vasoconstriction in the human coronary microcirculation: new evidence from myocardial contrast echocardiography

Circulation. 2013 Aug 6;128(6):598-604. doi: 10.1161/CIRCULATIONAHA.113.002937. Epub 2013 Jun 28.

Abstract

Background: Cocaine is a major cause of acute coronary syndrome, especially in young adults; however, the mechanistic underpinning of cocaine-induced acute coronary syndrome remains limited. Previous studies in animals and in patients undergoing cardiac catheterization suggest that cocaine constricts coronary microvessels, yet direct evidence is lacking.

Methods and results: We used myocardial contrast echocardiography to test the hypothesis that cocaine causes vasoconstriction in the human coronary microcirculation. Measurements were performed at baseline and after a low, nonintoxicating dose of intranasal cocaine (2 mg/kg) in 10 healthy cocaine-naïve young men (median age, 32 years). Postdestruction time-intensity myocardial contrast echocardiography kinetic data were fit to the equation y=A(1-e(-βt)) to quantify functional capillary blood volume (A), microvascular flow velocity (β), and myocardial perfusion (A×β). Heart rate, mean arterial pressure, and left ventricular work (2-dimensional echocardiography) were measured before and 45 minutes after cocaine. Cocaine increased mean arterial pressure (by 14±2 mm Hg [mean±SE]), heart rate (by 8±3 bpm), and left ventricular work (by 50±18 mm Hg·mL(-1)·bpm(-1)). Despite the increases in these determinants of myocardial oxygen demand, myocardial perfusion decreased by 30% (103.7±9.8 to 75.9±10.8 arbitrary units [AU]/s; P<0.01) mainly as a result of decreased capillary blood volume (133.9±5.1 to 111.7±7.7 AU; P<0.05) with no significant change in microvascular flow velocity (0.8±0.1 to 0.7±0.1 AU).

Conclusions: In healthy cocaine-naïve young adults, a low-dose cocaine challenge evokes a sizeable decrease in myocardial perfusion. Moreover, the predominant effect is to decrease myocardial capillary blood volume rather than microvascular flow velocity, suggesting a specific action of cocaine to constrict terminal feed arteries.

Keywords: cocaine; echocardiography; microcirculation; myocardial perfusion imaging.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Adult
  • Blood Flow Velocity / drug effects
  • Blood Flow Velocity / physiology
  • Blood Volume / drug effects
  • Blood Volume / physiology
  • Cardiotonic Agents / pharmacology
  • Cocaine / administration & dosage
  • Cocaine / adverse effects*
  • Cocaine / blood
  • Coronary Circulation / drug effects*
  • Coronary Circulation / physiology
  • Coronary Vessels / diagnostic imaging*
  • Coronary Vessels / drug effects*
  • Coronary Vessels / physiology
  • Dobutamine / administration & dosage
  • Echocardiography / methods
  • Echocardiography / standards
  • Humans
  • Male
  • Microvessels / diagnostic imaging
  • Microvessels / drug effects
  • Microvessels / physiology
  • Middle Aged
  • Reproducibility of Results
  • Vasoconstriction / drug effects*
  • Vasoconstrictor Agents / administration & dosage
  • Vasoconstrictor Agents / adverse effects*
  • Vasoconstrictor Agents / blood
  • Young Adult

Substances

  • Cardiotonic Agents
  • Vasoconstrictor Agents
  • Dobutamine
  • Cocaine