Thromboxane synthesis inhibitor in a beagle pup model of perinatal asphyxia.
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)
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Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510.
Stewart
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Petroff
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Duncan
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D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000378:metabolism / Q000503:physiopathology*; D001794:Blood Pressure; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004285:Dogs; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007231:Infant, Newborn; D009682:Magnetic Resonance Spectroscopy; D011725:Pyridines / Q000494:pharmacology*; D011897:Random Allocation; D013930:Thromboxane-A Synthase / Q000494:pharmacology*
D007093:Imidazoles; D011725:Pyridines; C037787:pirmagrel; D013930:Thromboxane-A Synthase