Cerebral responses to single and multiple cocaine injections in newborn sheep

Newborn infants exposed to cocaine near birth display a wide range of neurologic abnormalities, but the mechanism or mechanisms for these injuries remain unknown. We studied the cerebral effects of a single acute dose (4 mg/kg; n = 7) and multiple binge doses (4 mg/kg hourly for 5 h; n = 7) of i.v. cocaine in unancsthetized newborn (5 ± 1 d old) sheep. We measured cerebral blood flow, mean arterial blood pressure, arterial blood gases, and cerebral O₂ metabolism. Measurements were made at baseline; 30 s; and 5,15, and 60 min after a single injection of cocaine in the acute group and at the same time intervals after the 5th dose of cocaine in the binge group. CBF increased by 98 ± 68% (mean ± SD) at 30 s after a single acute dose and by 97 ± 94% at 30 s after the 5th of five hourly binge doses. Although it returned to baseline by 5 min in the acute group, cerebral blood flow remained elevated 5, 15, and 60 min after the 5th cocaine dose in the binge group. At 30 s, mean arterial blood pressure increased by 57 ± 21% in the acute group and 46 ± 15% in the binge group. In both groups, mean arterial blood pressure remained elevated at 5 min. Although no change occurred in cerebral O₂ metabolism in the acute group, an increase in cerebral O₂ consumption (7.4 ±1.3 mL/100 g/ min versus 5.5 ± 1.1 at baseline) was observed at 5 min in the binge group. Thus, injection of cocaine as a single acute dose or after multiple binge doses results in acute cerebral vasodilation and hypertension in newborn sheep. Acute cerebral vasodilation, when combined within hypertension, may partially explain the pathogenesis of cocaine-associated neonatal neurologic abnormalities.