Post‐hypoxic hypoperfusion is associated with suppression of cerebral metabolism and increased tissue oxygenation in near‐term fetal sheep
- 28 March 2006
- journal article
- Published by Wiley in The Journal of Physiology
- Vol. 572 (1), 131-139
- https://doi.org/10.1113/jphysiol.2005.100768
Abstract
Secondary cerebral hypoperfusion is common following perinatal hypoxia–ischaemia. However, it remains unclear whether this represents a true failure to provide sufficient oxygen and nutrients to tissues, or whether it is simply a consequence of reduced cerebral metabolic demand. We therefore examined the hypothesis that cerebral oxygenation would be reduced during hypoperfusion after severe asphyxia, and further, that the greater neural injury associated with blockade of the adenosine A1 receptor during the insult would be associated with greater hypoperfusion and deoxygenation. Sixteen near-term fetal sheep received either vehicle or 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) for 1 h, followed by 10 min of severe asphyxia induced by complete occlusion of the umbilical cord. Infusions were discontinued at the end of the occlusion and data were analysed for the following 8 h. A transient, secondary fall in carotid artery blood flow and laser Doppler flow was seen from approximately 1–4 h after occlusion (P < 0.001), with no significant differences between vehicle and DPCPX. Changes in laser Doppler blood flow were highly correlated with carotid blood flow (r2= 0.81, P < 0.001). Cortical metabolism was suppressed, reaching a nadir 1 h after occlusion and then resolving. Cortical tissue PO2 was significantly increased at 1, 2 and 3 h after occlusion compared to baseline, and inversely correlated with carotid blood flow (r2= 0.69, P < 0.001). In conclusion, contrary to our initial hypothesis, delayed posthypoxic hypoperfusion was associated with suppression of cerebral metabolism and increased tissue PO2, and was not significantly affected by preceding adenosine A1 blockade. These data suggest that posthypoxic hypoperfusion is actively mediated and reflects suppressed cerebral metabolism.Keywords
This publication has 41 references indexed in Scilit:
- Cerebral Oxygenation during Postasphyxial Seizures in Near-Term Fetal SheepJournal of Cerebral Blood Flow & Metabolism, 2005
- High-resolution neurometabolic coupling revealed by focal activation of visual neuronsNature Neuroscience, 2004
- Cerebral Metabolism during Cord Occlusion and Hypoxia in the Fetal Sheep: A Novel Method of Continuous Measurement Based on Heat ProductionThe Journal of Physiology, 2003
- Key Neuroprotective Role for Endogenous Adenosine A 1 Receptor Activation During Asphyxia in the Fetal SheepStroke, 2003
- Titration of Postischemic Cerebral Hypoperfusion by Variation of Ischemic Severity in a Murine Model of StrokeNeurosurgery, 1999
- The cardiovascular and cerebrovascular responses of the immature fetal sheep to acute umbilical cord occlusionThe Journal of Physiology, 1999
- Inhibitory Mechanisms in Cerebral Ischemia: a Brief ReviewNeuroscience & Biobehavioral Reviews, 1997
- Dramatic neuronal rescue with prolonged selective head cooling after ischemia in fetal lambs.JCI Insight, 1997
- Time course of intracellular edema and epileptiform activity following prenatal cerebral ischemia in sheep.Stroke, 1991
- Regulation of cerebral blood flow after asphyxia in neonatal lambs.Stroke, 1988