Comparison of cerebrovascular effects of intravenous cocaine injection in fetal, newborn, and adult sheep

Cocaine may cause stroke, intracranial hemorrhage, seizures, and neurobehav ioral abnormalities in fetuses, newborns, and adults, and there could be de velopmental and/or species differences in mechanisms for these cocaine-indu ced cerebrovascular effects. To evaluate developmental differences in respo nses to cocaine, we compared the cerebrovascular and metabolic responses to a 2 mg/kg iv cocaine dose in unanesthetized fetal (n = 8, previously repor ted, direct fetal injection), newborn (n = 6), and adult (n = 12) sheep. We measured cerebral blood flow, mean arterial blood pressure, and arterial a nd venous O-2 content, and we calculated cerebral O-2 consumption and cereb ral vascular resistance at baseline and at 30 s and at 5, 15, and 60 min af ter 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 adul t. Cerebral metabolic O-2 consumption increased 5 min after injection in th e fetus and newborn, but not until 15 min after injection in the adult. Art erial O-2 content decreased 5 min after injection in the fetus and 15 min a fter injection in the adult. We speculate that clinical differences in resp onse to cocaine injection may be explained, in part, by these developmental differences in the cerebrovascular and metabolic responses to cocaine.