Cardiovascular effects of cocaine: enhancement by yohimbine and atropine.
The cardiovascular effects of cocaine, alone and in combination with yohimbine and/or atropine, were studied in dogs anesthetized with pentobarbital sodium. All dogs were instrumented for the measurement of arterial blood pressure, left ventricular contractile force, left circumflex coronary artery blood flow, lead II ECG and heart rate. Dogs were divided into two groups; one group received no pretreatment, the other group was pretreated with atropine sulfate, 2 mg/kg. Both groups received two i.v. doses of cocaine, 1 mg/kg, approximately 3.5 hr apart. Thirty minutes before administration of the second cocaine dose, yohimbine, 0.25 mg/kg, i.v. was administered. In control animals which did not receive atropine or yohimbine, there was no difference in the cardiovascular responses to the two cocaine doses administered on this schedule. Administration of cocaine alone increased mean arterial blood pressure 9.6 +/- 2.2 mm Hg and increased the rate-pressure product, an index of myocardial oxygen consumption, 12.6 +/- 4.7%. Coronary blood flow was increased 13.1 +/- 4%. Yohimbine pretreatment significantly enhanced the cardiovascular actions of cocaine and this enhancement was most pronounced in the presence of atropine. When cocaine was administered after treatment with both atropine and yohimbine, mean arterial blood pressure was increased 44.2 +/- 7.2 mm Hg, heart rate was increased 30 +/- 7.9 beats/min and the rate-pressure product was increased by 72 +/- 10.1%, whereas coronary blood flow was increased only 42.8 +/- 12%. These data suggest that presynaptic alpha adrenergic and cholinergic muscarinic blockade may significantly increase the risk of cocaine-induced cardiovascular toxicity.
Wilkerson
R D
RD
Department of Pharmacology, Medical College of Ohio, Toledo.
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D019832:N-Methylscopolamine; D009638:Norepinephrine / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D012602:Scopolamine Derivatives / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology*
D012602:Scopolamine Derivatives; D015016:Yohimbine; D001285:Atropine; D003042:Cocaine; D019832:N-Methylscopolamine; D009638:Norepinephrine