Time course of direct cardiotoxic effects of high cocaine concentration in isolated rabbit heart.
Studies of acute cocaine cardiotoxicity are often confounded by the effects of cocaine on peripheral hemodynamics and an intact sympathetic nervous system. To study the direct effects of an acute dose of cocaine on heart, we used Langendorff-perfused isolated rabbit hearts. The hearts were attached to a Langendorff perfusion system through the aorta and were perfused with Krebs-Henseleit buffer. In nonpaced hearts, cocaine in concentrations of 10, 25, and 50 microM (reported to be in the range of drug concentrations lethal for humans) caused dose-dependent deterioration in heart contractility (decrease in +dP/dt, -dP/dt, and developed pressure) and coronary flow, when measured at 10, 20, and 30 min of the protocol. Cocaine 25 and 50 microM also caused a decrease in heart rate (HR). In paced hearts treated with cocaine 50 microM, early events included a progressive decrease in +dP/dt (by 15% vs. baseline at 20 s of perfusion and by 26% vs. baseline and 19% vs. control group at 30 s of perfusion; p < 0.05) and in -dP/dt (by 20% vs. baseline at 30 s of perfusion and by 25% vs. baseline and 15% vs. control group at 40 s of perfusion, p < 0.05). Decrease in HR (failure to pace) was observed only at 60 s of perfusion and averaged 20% versus both baseline and control group (p < 0.05). No changes in coronary flow were observed during the first 60 s after onset of cocaine administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Simkhovich
B Z
BZ
Heart Institute, Hospital of the Good Samaritan, Los Angeles, California 90017.
Kloner
R A
RA
Alker
K J
KJ
Giaconi
J
J
D000818:Animals; D002304:Cardiac Pacing, Artificial; D003042:Cocaine / Q000493:pharmacokinetics / Q000633:toxicity*; D003326:Coronary Circulation / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D011817:Rabbits
D003042:Cocaine