Delayed vasodilation and altered oxygenation after cerebral ischemia in fetal sheep

K. A. Marks, E. C. Mallard, I. Roberts, C. E. Williams, E. S. Sirimanne, B. Johnston, P. D. Gluckman, A. D. Edwards

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

The study investigated the hypothesis that delayed cerebral injury after transient cerebral ischemia is associated with vasoconstriction and decreased cerebral oxygenation. Eight chronically instrumented, late gestation fetal sheep were subjected to 30 rain of cerebral ischemia in utero. Cortical impedance (CI) and electrocorticogram (ECoG) were recorded to determine the time course of cellular dysfunction. Histologic outcome was assessed 4 d postischemia. Changes in cerebral vascular tone and oxygenation were observed during and for 4 d after the insult using near infrared spectroscopy to measure changes in total cerebral Hb ([tHb]), oxyhemoglobin ([Hbo2]), and oxidized cytochrome aa3 ([Cyto2]). Results are expressed as mean ± SEM, CI increased transiently during ischemia; then a delayed increase commenced 17.5 ± 2.3 h postischemia and peaked at 42.3 ± 2.4 h, ECoG was depressed during and after the insult. Seizures started 13.6 ± 3.0 h postinsult and persisted for 25.4 ± 3.2 h. Increases in [tHb] indicated two periods of cerebral vasodilation: immediately after early reperfusion, lasting 2.3 ± 0.4 h and peaking to 20 ± 2.0 μmol · L-1; and a later phase, commencing 12.8 ± 2.0 h postischemia, peaking to 43 ± 4.0 μmol · L-1 and lasting 43.1 ± 5.2 h. [Hbo2] was relatively elevated (18 ± 3.0 μmol · L-1) during d 4 postischemia, demonstrating a delayed increase in mean cerebral oxygen saturation, [Cyto2] fell during the insult (-0.7 ± 0.2 μmol · L-1); and, commencing at 28-30 h postischemia, fell progressively to reach a minimum of 5.0 ± 2.8 μmol · L-1 m at 78-80 h postischemia. A greater fall in [Cyto2] was related to worse cerebral injury (p < 0.05). Delayed cerebral injury is accompanied by vasodilation and increased mean cerebral oxygen saturation, although a progressive fall in [Cyto2] might indicate a fall in mitochondrial oxygenation, cell loss, or changes in tissue optical characteristics.

Original languageEnglish
Pages (from-to)48-54
Number of pages7
JournalPediatric Research
Volume39
Issue number1
DOIs
StatePublished - 1 Jan 1996
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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