Effect of long-term cocaine administration to pregnant ewes on fetal hemodynamics, oxygenation, and growth.
OBJECTIVE
To assess uterine and fetal blood flows by Doppler velocimetry and fetal growth and oxygenation in pregnant ewes treated daily with cocaine and to determine whether cocaine impairs fetal cardiac and cerebral reactivity.


METHODS
The study groups received 70 mg (n = 7) or 140 mg (n = 7) of cocaine and the control group (n = 7) received placebo injected intramuscularly daily on days 60-134. Hemodynamic data were measured at rest and during two acute hypoxic tests at cesarean delivery performed on day 134.


RESULTS
The fetal heart rate (FHR) and umbilical and uterine resistance indices (RIs) were higher in the cocaine groups than in the control group (FHR: 187 +/- 8 and 166 +/- 8 beats per minute at 83 and 123 days, respectively, in controls and 9-11% higher in cocaine groups; umbilical RI: 0.79 +/- 0.06, 0.60 +/- 0.04, and 0.52 +/- 0.06, at 83, 105, and 123 days, respectively, in controls and 11-17% higher in the cocaine groups [P < .01]; and uterine RI: 0.40 +/- 0.05, 0.40 +/- 0.04, and 0.37 +/- 0.04, at 83, 105, and 123 days, respectively, in controls and 13-35% higher in cocaine groups [P < .05]). At delivery on day 134, the following characteristics were found to be different in the cocaine groups: fetal weight (4.03 +/- 0.2 kg in controls and 15-21% lower in the cocaine groups [P < .02]), partial pressure of oxygen (26.5 +/- 1.4 mmHg in controls and 15-16% lower in cocaine groups [P < .05]), umbilical RI (0.40 +/- 0.03 in controls and 11-17% higher in cocaine groups [P < .01]), cerebral RI (0.61 +/- 0.03 in controls and 9-15% lower in cocaine groups [P < .01]), and cerebral-umbilical ratio (1.52 +/- 0.04 in controls and 22-23% lower in cocaine groups [P < .001]). During the hypoxic tests, the cerebral RI (P < .05) and the cerebral-umbilical ratio (P < .05) decreased significantly less in the two cocaine groups. The FHR response was reduced significantly in the two cocaine groups (P < .05).


CONCLUSIONS
Long-term exposure to cocaine induces uterine and fetal blood flow disorders, fetal growth restriction, and hypoxia. It reduces the capability of the cerebral vessels to vasodilate and the heart rate to increase during acute hypoxia.
Arbeille
P
P
Département de Médecine Nucléaire et Ultrasons, Institut National de la Santé et de la Recherche Médicale, CHU Hôpital Trousseau, Tours, France. arbeille@med.univ-tours.fr
Maulik
D
D
Salihagic
A
A
Locatelli
A
A
Lansac
J
J
Platt
L D
LD
D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003042:Cocaine / Q000633:toxicity*; D019970:Cocaine-Related Disorders; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced*; D005311:Fetal Hypoxia / Q000139:chemically induced*; D006340:Heart Rate, Fetal / Q000187:drug effects; D021041:Placental Circulation / Q000187:drug effects*; D011247:Pregnancy; D012756:Sheep; D018608:Ultrasonography, Doppler
D003042:Cocaine