During perinatal
asphyxia, cerebral blood flow is markedly reduced in the gray and white matter of the telencephalon. Since previous work has implicated
prostaglandins in the control of blood flow, we tested the hypothesis that a
thromboxane synthesis inhibitor would improve cerebral blood flow and blunt the metabolic alterations that accompany
asphyxia. Forty-three newborn beagles 2-7 days old were anesthetized, ventilated, and randomized to insult (5 minutes of
asphyxia) or no insult and received treatment with either the
thromboxane synthesis inhibitor
CGS 13080 (CIBA-GEIGY Corp.) (0.06 mg/kg/hr i.v. infusion) or saline. Cerebral blood flow was measured in 25 pups. Pups received treatment 30 minutes before insult or no insult. In pups randomized to insult and receiving saline, cerebral blood flow increased during insult in the medulla but decreased elsewhere. Pups randomized to insult and treated with
thromboxane synthesis inhibitor had increased cerebral blood flow during insult in all cerebral regions studied. In addition, these pups experienced a significantly higher incidence of intraventricular
hemorrhage than did pups randomized to insult and receiving saline. In other experiments with 18 pups, brain extracts were prepared for
proton nuclear magnetic resonance spectral analysis of high-energy phosphorylated compounds and
lactate levels. In pups exposed to insult and receiving saline, mean +/- SD
phosphocreatine concentration fell from 1.9 +/- 0.1 to 0.4 +/- 0.1 mmol/kg,
lactate concentration increased from 2.0 +/- 0.5 to 3.3 +/- 0.4 mmol/kg, and the calculated pH fell 0.8 units. There were no differences between groups.(ABSTRACT TRUNCATED AT 250 WORDS)