Effects of indomethacin upon cerebral hemodynamics of newborn pigs

Charles Leffler, David W. Busija, Anthony M. Fletcher, Donathan G. Beasley, Jack R. Hessler, Robert S. Green

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Treatment of unanesthetized newborn pigs with indomethacin trihydrate (5 ± 1 mg/kg, intravenous) decreased cerebral blood flow uniformly throughout the brain by 18-28% without changing cardiac output, arterial pressure, or arterial blood gases and pH. Breathing 10% O2, 9% CO2 with the balance N2 (hypoxia/hypercapnia) caused cerebral blood flow to increase from 102 ± 12 to 218 ± 19 ml/100 g.min. Intravenous administration of indomethacin during hypoxia/hypercapnia caused a uniform decrease in cerebral flow throughout the brain to levels (94 ± 5 ml/100 g.min) indistinguishable from those when the piglet was breathing ambient air. Further, 2.5 h later, the cerebral hyperemia caused by hypoxia/hypercapnia was attenuated markedly (129 ± 19 ml/100 g.min). Vehicle treatment did not alter resting cerebral blood flow or cerebral hyperemia in response to hypoxia/hypercapnia. Measurements of 6-keto-prostaglandin Fta, thromboxane B2, and prostaglandin E2 demonstrated that intravenously administered indomethacin crossed the blood-brain barrier of newborn pigs in sufficient quantity to inhibit prostanoid release into the cerebrospinal fluid passing over the surface of the brain. The mechanism by which indomethacin reduces cerebral blood flow and attenuates cerebral hyperemia cannot be determined from the present experiments. We conclude that intravenous administration of indomethacin decreases cerebral blood flow and attenuates cerebral hyperemia induced by severe, combined hypoxia/hypercapnia in newborn pigs.

Original languageEnglish (US)
Pages (from-to)1160-1164
Number of pages5
JournalPediatric Research
Volume19
Issue number11
DOIs
StatePublished - Jan 1 1985

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Cerebrovascular Circulation
Hypercapnia
Indomethacin
Hyperemia
Swine
Hemodynamics
Intravenous Administration
Prostaglandins
Brain
Respiration
Thromboxane B2
Blood-Brain Barrier
Dinoprostone
Cardiac Output
Cerebrospinal Fluid
Arterial Pressure
Gases
Air
Hypoxia
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

Cite this

Leffler, C., Busija, D. W., Fletcher, A. M., Beasley, D. G., Hessler, J. R., & Green, R. S. (1985). Effects of indomethacin upon cerebral hemodynamics of newborn pigs. Pediatric Research, 19(11), 1160-1164. https://doi.org/10.1203/00006450-198511000-00009

Effects of indomethacin upon cerebral hemodynamics of newborn pigs. / Leffler, Charles; Busija, David W.; Fletcher, Anthony M.; Beasley, Donathan G.; Hessler, Jack R.; Green, Robert S.

In: Pediatric Research, Vol. 19, No. 11, 01.01.1985, p. 1160-1164.

Research output: Contribution to journalArticle

Leffler, C, Busija, DW, Fletcher, AM, Beasley, DG, Hessler, JR & Green, RS 1985, 'Effects of indomethacin upon cerebral hemodynamics of newborn pigs', Pediatric Research, vol. 19, no. 11, pp. 1160-1164. https://doi.org/10.1203/00006450-198511000-00009
Leffler, Charles ; Busija, David W. ; Fletcher, Anthony M. ; Beasley, Donathan G. ; Hessler, Jack R. ; Green, Robert S. / Effects of indomethacin upon cerebral hemodynamics of newborn pigs. In: Pediatric Research. 1985 ; Vol. 19, No. 11. pp. 1160-1164.
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