Propranolol blocks cocaine-induced cerebral vasodilation in newborn sheep

Objective: The objective of this study was to test the hypothesis that coca ine-induced cerebral vasodilation in newborn sheep is mediated via beta-adr energic receptor activation. Design: The cerebral effects of a single intravenous injection of cocaine ( 4 mg/kg) given 30 mins after pretreatment with propranolol(1 mg/kg) were st udied and compared with the results from a previous study using an identica l cocaine protocol without propranolol pretreatment. Subjects: Seven chronically catheterized, unanesthetized newborn sheep (6+/ -1 days old). Measurements: Cerebral blood flow using radiolabeled microspheres, mean art erial blood pressure (MAP), heart rate, and cerebral arterial and venous ox ygen content were measured at baseline, after administration of propranolol , and 0.5, 5, 15, and 60 mins after cocaine injection. Cerebrovascular resi stance was calculated as the MAP divided by the cerebral blood flow. Main Results: Propranolol injection alone caused no systemic or cerebral ph ysiologic changes other than an 11 +/- 2% (mean +/-:SEM) decrease in heart rate, which was sustained after cocaine injection, In contrast to previous studies showing cerebral vasodilation (25% decrease in cerebrovascular resi stance) and acute hypertension (57% increase in MAP) 30 sees after cocaine injection, there were no changes in cerebrovascular resistance after cocain e injection and after propranolol pretreatment and there was only a 23 +/-: 7% increase in MAP 30 sees after injection, with a return to baseline by 15 mins. Cocaine and norepinephrine levels were similar to those previously r eported in the newborn sheep after an injection of 4 mg/kg cocaine. Conclusion: Propranolol blocks cocaine-induced cerebral vasodilation and bl unts the acute hypertension in newborn sheep, suggesting that cocaine's cer ebrovascular effects in the developing brain are mediated, at least in part , by beta-adrenergic receptor activation.