Relationship between evolving epileptiform activity and delayed loss of mitochondrial activity after asphyxia measured by near-infrared spectroscopy in preterm fetal sheep.
Early onset cerebral hypoperfusion after birth is highly correlated with neurological injury in premature infants, but the relationship with the evolution of injury remains unclear. We studied changes in cerebral oxygenation, and cytochrome oxidase (CytOx) using near-infrared spectroscopy in preterm fetal sheep (103-104 days of gestation, term is 147 days) during recovery from a profound asphyxial insult (n= 7) that we have shown produces severe subcortical injury, or sham asphyxia (n= 7). From 1 h after asphyxia there was a significant secondary fall in carotid blood flow (P < 0.001), and total cerebral blood volume, as reflected by total haemoglobin (P < 0.005), which only partially recovered after 72 h. Intracerebral oxygenation (difference between oxygenated and deoxygenated haemoglobin concentrations) fell transiently at 3 and 4 h after asphyxia (P < 0.01), followed by a substantial increase to well over sham control levels (P < 0.001). CytOx levels were normal in the first hour after occlusion, was greater than sham control values at 2-3 h (P < 0.05), but then progressively fell, and became significantly suppressed from 10 h onward (P < 0.01). In the early hours after reperfusion the fetal EEG was highly suppressed, with a superimposed mixture of fast and slow epileptiform transients; overt seizures developed from 8 +/- 0.5 h. These data strongly indicate that severe asphyxia leads to delayed, evolving loss of mitochondrial oxidative metabolism, accompanied by late seizures and relative luxury perfusion. In contrast, the combination of relative cerebral deoxygenation with evolving epileptiform transients in the early recovery phase raises the possibility that these early events accelerate or worsen the subsequent mitochondrial failure.
Department of Physiology, University of Auckland, Private Bag 92019, Auckland, New Zealand. l.bennet@auckland.ac.nz
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L
Bennet
V
V
Roelfsema
P
P
Pathipati
J S
JS
Quaedackers
A J
AJ
Gunn
D000818:Animals; D001237:Asphyxia / Q000196:embryology* / Q000503:physiopathology*; D004827:Epilepsy / Q000196:embryology* / Q000503:physiopathology*; D005865:Gestational Age; D028361:Mitochondrial Diseases / Q000196:embryology* / Q000503:physiopathology*; D010100:Oxygen / Q000378:metabolism*; D012756:Sheep; D013055:Spectrophotometry, Infrared / Q000379:methods
D010100:Oxygen