Cocaine cardiotoxicity differs markedly in isolated hearts of two strains of rats exhibiting phenotypic differences in sensitivity to seizures.
Isolated hearts from two strains of rats bred for sensitivity or resistance to amygdala kindling that also exhibit, in vivo, differential sensitivity to the cardiotoxicity of cocaine were studied. The goal was to determine if the differential cardiotoxic sensitivity was due, at least in part, to intrinsic strain-dependent differences in the heart. The Langendorff preparation was used (n=8 per strain). Hearts were perfused with increasing concentrations of cocaine (5 x 10(-6), 1 x 10(-5), 5 x 10(-5), 1 x 10(-4), and 5 x 10(-4) M) for 5 min with a 5 min washout between exposure to successive concentrations. Consistent with in vivo observations, hearts from genetically slow amygdala kindling rats (Slow) required lower cocaine doses to develop cardiac arrhythmias and arrest as compared to the hearts from genetically fast amygdala kindling rats (Fast). At 5 x 10(-5) M cocaine arrhythmias occurred in 38% (3/8) Slow and 0% Fast hearts. Five of 8 Slow hearts and none of 8 Fast hearts were arrested by 10(-4) M cocaine. Arrest in Fast hearts occurred only with 5 x 10(-4) M cocaine. Cocaine constricted coronary arteries (no significant difference between strains). On the other hand, coronary arteries of Slow but not Fast hearts dilated during cocaine washout after perfusion with all but the highest concentration of cocaine. We conclude that factors intrinsic to the heart and coronary artery influence the sensitivity or response of these structures to cocaine.
Heavner
J E
JE
Anesthesiology, Texas Tech University Health Sciences Center, Lubbock 79430, USA. anejeh@ttuhsc.edu
Shi
B
B
Inners-McBride
K
K
Asimakis
G
G
Wang
M J
MJ
McIntyre
D C
DC
D000679:Amygdala; D000818:Animals; D001794:Blood Pressure; D003042:Cocaine / Q000008:administration & dosage / Q000633:toxicity*; D003331:Coronary Vessels / Q000502:physiology; D003971:Diastole; D004562:Electrocardiography; D006331:Heart Diseases / Q000139:chemically induced* / Q000235:genetics*; D006339:Heart Rate; D007696:Kindling, Neurologic; D008297:Male; D010641:Phenotype; D051381:Rats; D012640:Seizures / Q000235:genetics*; D013997:Time Factors; D016277:Ventricular Function, Left
D003042:Cocaine