Toxic effects of cocaine to the cardiovascular system in conscious and anesthetized rats and rabbits: evidence for a direct effect on the myocardium.
The cardiovascular toxicity of cocaine is complex because it has local anesthetic properties, central nervous system stimulatory effects, as well as cardiac effects. Recreational use of this drug has increased recently, but the precise mechanism of sudden cardiac death induced by cocaine is not known. The primary objective of this work was to test for a direct cardiovascular toxicity of cocaine. Rats and rabbits were anesthetized, and the femoral vein and artery were cannulated for drug infusion and blood pressure monitoring. Different doses of cocaine (0.3, 1, 3, 10 mg/kg) were infused. For conscious animal experiments, the animals were allowed to recover from the anesthesia and then were subjected to cocaine. Low doses of cocaine (0.3 and 1 mg/kg) increased systolic as well as diastolic pressure in conscious rats and rabbits. In anesthetized rats and rabbits, the same dose of cocaine increased blood pressure with a decrease in heart rate. With the high doses of cocaine (3 and 10 mg/kg), all cardiac parameters were reduced in both rats and rabbits. In isolated rabbit hearts, cocaine decreased all cardiac parameters. Based on the fact that high doses of cocaine severely depressed all cardiac parameters and its effect on the isolated heart, cocaine-induced sudden cardiac death appears to be due to a primary effect on the myocardium.
Rhee
H M
HM
Department of Pharmacology, Oral Roberts University School of Medicine, Tulsa, Oklahoma 74137.
Valentine
J L
JL
Lee
S Y
SY
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D003042:Cocaine / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D010424:Pentobarbital; D010477:Perfusion; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects; D014520:Urethane
D014520:Urethane; D010424:Pentobarbital; D003042:Cocaine