Estrogen mediates the pregnancy-enhanced cardiotoxicity of cocaine in the 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 progesterone.


METHODS
Hearts excised from 65 female Sprague-Dawley rats were attached to a Langendorff apparatus for measurement of left ventricular systolic pressure, heart rate, and contractility. Before excision, the animals were assigned to one of five groups: 1) nonpregnant, 2) pregnant, 3) nonpregnant pretreated with progesterone, 4) nonpregnant pretreated with estrogen, and 5) nonpregnant pretreated with estrogen 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 pressure and a 39.7% decrease in contractility for the highest dose). Although pre-treatment with estrogen, alone or with progesterone, resulted in responses similar to those seen in pregnant animals, progesterone 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 simulate changes by pretreating the animals with estrogen. Perhaps the enhanced cardiotoxicity of cocaine in pregnancy is partially mediated by estrogen.
Kurtzman
J T
JT
Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill.
Thorp
J M
JM
Spielman
F J
FJ
Perry
S
S
Mueller
R A
RA
Cefalo
R C
RC
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000502:physiology*; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D010477:Perfusion; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects / Q000502:physiology; D011374:Progesterone / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
D004967:Estrogens; D011374:Progesterone; D003042:Cocaine