Relationship between evolving epileptiform activity and delayed loss of mitochondrial activity after asphyxia measured by near-infrared spectroscopy in preterm fetal sheep
Relationship between evolving epileptiform activity and delayed loss of mitochondrial activity after asphyxia measured by near-infrared spectroscopy in preterm fetal sheep
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DOI：
10.1113/jphysiol.2006.105197
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发表时间：
2006-04-01
影响因子：
5.5
通讯作者：
Gunn, AJ
中科院分区：
文献类型：
--
作者：
Bennet, L;Roelfsema, V;Gunn, AJ
早产儿出生后早期脑低灌注与神经损伤密切相关，但与损伤演变的关系尚不清楚。我们用近红外光谱分析技术研究了早产羊(妊娠103-104天，足月147天)在严重窒息后(n=7)恢复期间脑氧合和细胞色素氧化酶(CytOx)的变化。从窒息后1小时开始，颈动脉血流量(P<；0.001)和总脑血流量(P<；0.005)显著下降，72小时后才部分恢复。脑内氧合(氧合和去氧血红蛋白浓度之差)在窒息后3和4小时短暂下降(P<；0.01)，随后显著增加，远高于假手术对照组水平(P<；0.001)。CytOx在脑缺血后1h开始恢复正常，2~3h高于假手术对照组(P<；0.05)，但随后逐渐下降，10h后显著降低(P<；0.01)。在再灌流后早期，胎儿脑电受到高度抑制，出现快速和慢速癫痫样瞬变的叠加；明显的癫痫发作发生在8+/-0.5h。这些数据强烈表明，严重窒息导致线粒体氧化代谢的延迟和进行性丧失，伴随着晚期癫痫发作和相对奢侈的灌流。相反，在早期恢复阶段，大脑相对脱氧和不断演变的癫痫样瞬变相结合，增加了这些早期事件加速或恶化随后线粒体衰竭的可能性。
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.