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 min 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 ± 3.0μmol·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 ± 2.8μmol·L-1 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.
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Abbreviations
- ECoG:
-
electrocorticogram
- CI:
-
cortical impedance
- NIRS:
-
near infrared spectroscopy
- [tHb]:
-
concentration of total cerebral Hb
- [Hbo2]:
-
concentration of oxyhemoglobin
- [Cyto2]:
-
concentration of oxidized cytochromeaa3
- CBF:
-
cerebral blood flow
- MAP:
-
mean arterial pressure
- Paco2:
-
partial pressure of arterial CO2
- Pao2:
-
parital pressure of arterial O2
- Sao2:
-
arterial oxygen saturation
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Acknowledgements
The authors are indebted to Dr. Mark Cope and Professor David Delpy at University College Hospital, London, for measuring the differential optical path length factor in the fetal sheep brain and to Dr. Chris Cooper for valuable discussion.
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Supported by The Wellcome Trust, the Garfield Weston Foundation, and the Health Research Council of New Zealand.
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Marks, K., Mallard, E., Roberts, I. et al. Delayed Vasodilation and Altered Oxygenation after Cerebral Ischemia in Fetal Sheep. Pediatr Res 39, 48–54 (1996). https://doi.org/10.1203/00006450-199601000-00007
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DOI: https://doi.org/10.1203/00006450-199601000-00007
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