The role of prostanoids in autoregulation of cerebral blood flow (CBF) of the newborn is unclear. We hypothesized that prostanoids not only exhibit cerebral vasoactive properties, but also play an important role in setting the limits of autoregulation of CBF in the newborn. / Consequently, in the newborn piglet, we determined the effects of prostaglandins (PGs), PGE$ sb1$, PGE$ sb2$, PGF$ sb{2 alpha}$ and PGI$ sb2$, on CBF, and compared their vasoactive action on isolated internal carotid and basilar arteries of newborns and adults. Cerebrovascular prostanoid concentrations were also measured as a function of systemic blood pressure (BP), in animals subjected or not to prostanoid synthesis inhibition, using ibuprofen. Finally, we examined in the preterm infant the effects of indomethacin on CBF velocity (CBFV) during clinical procedures (endotracheal suctioning) known to increase BP and CBFV concomitantly. / All major cerebrovascular PGs (physiologically relevant doses) increased CBF, and contracted minimally isolated arteries. These effects were most evident for PGF$ sb{2 alpha}$, the most effective adult vasoconstrictor PG. / During hypotension, sagittal sinus concentrations of thromboxane exhibited the highest increase of all prostanoids. However, during hypertension, PGE, PGF$ sb{2 alpha}$, and 6-keto-PGF$ sb{1 alpha}$ increased, without changes in TXB$ sb2$. Ibuprofen, inhibited the changes in prostanoids that occurred as a function of BP, and widened CBF autoregulation from 50-90 mm Hg to 35-117 mm Hg of BP. Therefore, the potent vasoconstrictor, thromboxane, contributed to set the lower limit of the CBF autoregulatory range to 50 mm Hg of BP; and PGs (which increase newborn CBF) contributed to the pressure-passivity of CBF above 90 mm Hg. / In the preterm newborn infant, indomethacin attenuated the increases in CBFV that occur with endotracheal suctioning; thus, in accord with studies on animals subjected to changes in BP. / In conclusion, PGs possess minimal cerebral vasocontractile activity in the newborn. The findings confirm our hypothesis that prostanoids contribute significantly in establishing the range of CBF autoregulation of the newborn, which is principally narrowed at its upper limit compared to that of the adult. Thus, the difference in the CBF autoregulatory range of the newborn and adult animal appears to result mainly from age-related differences in the effects of PGs on cerebral hemodynamics. Finally, ibuprofen may provide therapeutic modes to prevent hemorrhagic and ischemic encephalopathies of the newborn.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.75940 |
| Date | January 1989 |
| Creators | Chemtob, Sylvain |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Pharmacology and Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000909512, proquestno: AAINL52381, Theses scanned by UMI/ProQuest. |
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