Brain Vasoactive Effects of Phenobarbital during Hypertension and Hypoxia in Newborn Pigs

ABSTRACT: Phenobarbital in anticonvulsant concentrations has been shown to lower cerebral blood flow (CBF) during hypertension and to reduce the incidence of intraventricular hemorrhage in newborn beagles after hypertensive insult. We proposed that hypoxic dilatation of brain blood vessels might alter the effect of phenobarbital (PBS) on blood flow during hypertension. Thus, in 14 control and nine PBS-treated 1– to 2-d-old newborn piglets, the radioactive microsphere technique was used to determine CBF during 1) steady state (SS), 2) hypertension (HT), and 3) HT plus hypoxia of 5 min duration. In seven controls and in four PBS-treated piglets, CBF was also determined during recovery from hypoxia. PBS was infused after SS in a 20-mg/kg dose, and serum levels were obtained 30 min later. Blood pressures were not significantly different between groups when compared during SS, HT, hypoxia, and recovery. Similarly, pH, Po2, and Pco2were not significantly different between groups when compared during normoxia and hypoxia, and hematocrits were maintained by transfusions after reference sample withdrawals. CBF in control animals increased significantly during HT and remained significantly higher than SS values throughout the 5 min of hypoxia and into the recovery period. In PBS-treated piglets, however, there was no significant increase in CBF during HT. Blood flows also stayed at SS levels during HT plus 5 min hypoxia and recovery from hypoxia. Thus, in newborn piglets, PBS lowered CBF during HT. Furthermore, this blood flow lowering effect persisted during hypoxia, preventing compensatory increases in CBF that might have otherwise occurred. Although this may explain why PBS might be useful in preventing hemorrhages that result during hyperemia, further studies will determine if PBS pretreatment results in reduced oxygen delivery to brain tissues during hypoxia.