Acute cardiotoxic effects of cocaine and a hyperadrenergic state in anesthetized dogs.
The purpose of this study was to determine whether a subthreshold dose of cocaine (one that is well-tolerated in a resting state with no significant hemodynamic changes) causes cardiotoxic responses when superimposed upon a subthreshold infusion of norepinephrine. Adult mongrel dogs were anesthetized, instrumented and assigned to one of five treatment groups: saline control, norepinephrine infusion (0.75 microgram/kg/min, i.v. for 60 min); cocaine (5.0 mg/kg, i.v. bolus); combination of cocaine (0.5 mg/kg) or (5.0 mg/kg) with the last 45 min of norepinephrine infusion. The combination groups exhibited increased blood pressure and contractility (dP/dt), and a greater variety and frequency of arrhythmias. Cocaine did not increase plasma catecholamine levels beyond norepinephrine alone. There were significantly more contraction band lesions/mm2 with cocaine in combination with norepinephrine than in any of the individual treatment groups. These data indicate that, even in anesthetized animals, a well-tolerated dose of cocaine may become toxic when superimposed on an excited or hyperadrenergic state with elevated levels of norepinephrine.
Department of Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha 68198-6395.
D J
DJ
Keller
G L
GL
Todd
D000758:Anesthesia; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D003042:Cocaine / Q000633:toxicity*; D004285:Dogs; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D009206:Myocardium / Q000473:pathology; D009638:Norepinephrine / Q000633:toxicity*; D013564:Sympathetic Nervous System / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D002395:Catecholamines; D003042:Cocaine; D009638:Norepinephrine