Hemodynamic and cerebral blood flow effects of cocaine, cocaethylene and benzoylecgonine in conscious and anesthetized fetal lambs.
We studied hemodynamic responses to cocaine and two metabolites, cocaethylene (CE) and benzoylecgonine (BE), in five conscious ewes and fetuses, which were chronically instrumented to measure maternal and fetal aortic pressures, uterine artery blood flow (Qutr) and fetal common carotid artery blood flow (Qcar) to estimate cerebral blood flow. Conscious ewes of 121 to 128 days' (mean, 124 days) gestation received 1.0 mg/kg i.v. of cocaine (n = 12 doses), CE (n = 14) or BE (n = 12) and responses were compared to seven additional ewes and fetuses at 115 to 127 days' (mean, 122 days) gestation each given one 1.0 mg/kg i.v. of cocaine dose while anesthetized with halothane. In conscious ewes, cocaine, CE and BE all caused maternal and fetal hypertension. Qutr decreased 31% after cocaine, increased 37% after CE and was unaffected by BE. Cocaine induced fetal hypoxemia; fetal arterial blood gas tensions were unaffected by CE or BE. Fetal Qcar was reduced 51% at peak effect by cocaine (57 +/- 8 to 28 +/- 6 ml/min) and 46% by CE (65 +/- 7 to 33 +/- 6 ml/min), and was unaffected by BE because of variable subject response, although all three drugs increased calculated fetal cerebral vascular resistance. The cocaine-induced changes were attenuated or abolished in anesthetized sheep. Fetal/maternal peak serum concentrations were 100% for CE and only 2% for BE; amniotic fluid concentrations of CE were 10-fold higher than both fetal and maternal serum concentrations. Cocaine and cocaine metabolites have important effects on maternal and fetal hemodynamics and fetal cerebral blood flow which, for CE and BE, are not dependent on decreased uterine blood flow or fetal hypoxemia.
Department of Pediatrics, Wyler Children's Hospital, University of Chicago, Illinois.
R F
RF
Covert
M D
MD
Schreiber
I R
IR
Tebbett
L J
LJ
Torgerson
D000653:Amniotic Fluid / Q000378:metabolism; D000758:Anesthesia; D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000196:embryology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D003243:Consciousness; D005260:Female; D005333:Fetus / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced; D014179:Neurotransmitter Uptake Inhibitors / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000139:chemically induced; D012756:Sheep; D014159:Transducers; D014465:Ultrasonics; D014599:Uterus / Q000098:blood supply; D014655:Vascular Resistance / Q000187:drug effects
D014179:Neurotransmitter Uptake Inhibitors; C005618:benzoylecgonine; C066444:cocaethylene; D003042:Cocaine