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 in juries remain unknown. We studied the cerebral effects of a single acu te dose (4 mg/kg; n = 7) and multiple binge doses (4 mg/kg hourly for 5 h; n = 7) of i.v. cocaine in unanesthetized newborn (5 +/- 1 d old) sheep. We measured cerebral blood flow, mean arterial blood pressure, arterial blood gases, and cerebral Oz metabolism. Measurements were ma de at baseline; 30 s; and 5, 15, and 60 min after a single injection o f 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% (m ean +/- 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 ba seline by 5 min in the acute group, cerebral blood flow remained eleva ted 5, 15, and 60 min after the 5th cocaine dose in the binge group. A t 30 s, mean arterial blood pressure increased by 57 +/- 21% in the ac ute group and 46 +/- 15% in the binge group. In both groups, mean arte rial blood pressure remained elevated at 5 min. Although no change occ urred in cerebral O-2 metabolism in the acute group, an increase in ce rebral O-2 consumption (7.4 +/- 1.3 mL/100 g/ min versus 5.5 +/- 1.1 a t baseline) was observed at 5 min in the binge group. Thus, injection of cocaine as a single acute dose or after multiple binge doses result s in acute cerebral vasodilation and hypertension in newborn sheep. Ac ute cerebral vasodilation, when combined within hypertension, may part ially explain the pathogenesis of cocaine-associated neonatal neurolog ic abnormalities.