ESTROGEN MEDIATES THE PREGNANCY-ENHANCED CARDIOTOXICITY OF COCAINE INTHE ISOLATED-PERFUSED RAT-HEART

Objective: To determine whether pregnancy enhances cocaine toxicity in the isolated perfused whole rat heart model and whether this enhanced toxicity can be simulated by pre-treatment with either estrogen or pr ogesterone. Methods: Hearts excised from 65 female Sprague-Dawley rats were attached to a Langendorff apparatus for measurement of left vent ricular systolic pressure, heart rate, and contractility. Before excis ion, the animals were assigned to one of five groups: 1) nonpregnant, 2) pregnant, 3) nonpregnant pretreated with progesterone, 4) nonpregna nt pretreated with estrogen, and 5) nonpregnant pretreated with estrog en and progesterone. Each group was exposed serially to the following cocaine concentrations: 5 X 10(-6), 1 X 10(-5), and 6 x 10(-5) mol/L. Results: Heart rate declined at all doses of cocaine (9.2, 6.9, and 31 .0%, respectively). The lowest dose of cocaine had positive inotropic effects, with a 23.2% increase in left ventricular pressure and a 15.3 % increase in contractility. Exposure to the two higher doses resulted in negative inotropic effects (a 24.8% decrease in left ventricular p ressure and a 39.7% decrease in contractility for the highest dose). A lthough pre-treatment with estrogen, alone or with progesterone, resul ted in responses similar to those seen in pregnant animals, progestero ne pre-treatment alone failed to do so. Conclusions: Cocaine displayed cardiotoxicity in isolated rat hearts similar to that in other animal models. This toxicity was enhanced by pregnancy. We were able to simu late changes by pretreating the animals with estrogen. Perhaps the enh anced cardiotoxicity of cocaine in pregnancy is partially mediated by estrogen.