Cardiovascular effects of acute and chronic cocaine administration in pregnant and nonpregnant rabbits.
The effects of cocaine administration on cardiovascular parameters were studied in anesthetized nonpregnant and pregnant rabbits with no prior exposure to cocaine and in pregnant rabbits repeatedly administered cocaine (4 mg/kg, bid, iv) for 15-20 days prior to the experiment. Rabbits were instrumented to determine the effects of cocaine on blood pressure, heart rate, and organ blood flows. Administration of the 1 and 2 mg/kg doses of cocaine increased blood pressure and decreased heart rate in both pregnant and nonpregnant rabbits. In contrast, the 4 mg/kg dose of cocaine caused reductions in both blood pressure and heart rate. Cocaine (1, 2, and 4 mg/kg, iv) also caused dose-dependent reductions in organ blood flows. Interestingly, cocaine did not affect uterine blood flow in the nonpregnant rabbits, whereas uterine and placental flows were markedly reduced in both groups of pregnant rabbits. Chronic treatment with cocaine caused a significant increase in the basal blood flow to the placenta and spleen, and a more precipitous decrease in blood flow in both organs in response to an acute injection of cocaine. The chronically treated rabbits also had a greater incidence of cardiac arrhythmias in response to an acute injection of cocaine (4 mg/kg, iv). Rabbits that received repeated administrations of cocaine experienced more prolonged reductions in blood flow than rabbits with no prior exposure to cocaine. These studies show that cocaine has marked effects on organ blood flows and that pregnancy and repeated prior administrations of cocaine can enhance these effects.
Sutliff
R L
RL
Department of Pharmacology, Medical College of Pennsylvania and Hahneman University, 3200 Henry Avenue, Philadelphia, Pennsylvania, 19129, USA. sutlifrl@uc.edu
Gayheart-Walsten
P A
PA
Snyder
D L
DL
Roberts
J
J
Johnson
M D
MD
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008863:Microspheres; D010920:Placenta / Q000098:blood supply / Q000187:drug effects; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000139:chemically induced / Q000503:physiopathology; D011270:Pregnancy, Animal / Q000187:drug effects*; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014599:Uterus / Q000098:blood supply / Q000187:drug effects
D003042:Cocaine