title: Comparison of cerebrovascular effects of intravenous cocaine injection in fetal, newborn, and adult sheep.
abstract: Cocaine may cause stroke, intracranial hemorrhage, seizures, and neurobehavioral abnormalities in fetuses, newborns, and adults, and there could be developmental and/or species differences in mechanisms for these cocaine-induced cerebrovascular effects. To evaluate developmental differences in responses to cocaine, we compared the cerebrovascular and metabolic responses to a 2 mg/kg iv cocaine dose in unanesthetized fetal (n = 8, previously reported, direct fetal injection), newborn (n = 6), and adult (n = 12) sheep. We measured cerebral blood flow, mean arterial blood pressure, and arterial and venous O(2) content, and we calculated cerebral O(2) consumption and cerebral vascular resistance at baseline and at 30 s and at 5, 15, and 60 min after cocaine injection. Cerebral blood flow increased 5 min after injection in the fetus and newborn, but not until 15 min in the adult. In the fetus, cocaine caused a transient cerebral vasoconstriction at 30 s; in all three groups, cocaine caused cerebral vasodilation, which was delayed in the adult. Cerebral metabolic O(2) consumption increased 5 min after injection in the fetus and newborn, but not until 15 min after injection in the adult. Arterial O(2) content decreased 5 min after injection in the fetus and 15 min after injection in the adult. We speculate that clinical differences in response to cocaine injection may be explained, in part, by these developmental differences in the cerebrovascular and metabolic responses to cocaine.
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: R
authors.initials: R
authors.lastname: Robinson
authors.forename: H
authors.initials: H
authors.lastname: Iida
authors.forename: T P
authors.initials: TP
authors.lastname: O'Brien
authors.forename: M A
authors.initials: MA
authors.lastname: Pane
authors.forename: R J
authors.initials: RJ
authors.lastname: Traystman
authors.forename: C A
authors.initials: CA
authors.lastname: Gleason
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000196:embryology; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D005333:Fetus; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D010313:Partial Pressure; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D002245:Carbon Dioxide; D003042:Cocaine; D010100:Oxygen