Cerebral O2 Supply Thresholds for the Preservation of Electrocortical Brain Activity During Hypotension in Near-Term-Born Lambs

Abstract

The fetal brain develops rapidly during the last trimester of pregnancy. Therefore, the brain of infants who are born preterm is vulnerable to changes in oxygen and nutrient supply in the neonatal period. The objective was to determine the effect of gestational age (GA) on the cerebral O 2 supply threshold level for preservation of brain function during hypotension in nearterm-born lambs. Lambs were delivered at 141 or 127 d of gestation Approximately 2% of all newborns in the Netherlands are born before 32 completed weeks of gestation. Although mortality rates have decreased over the past 15 y, long-term morbidity has not changed (1). Because the fetal brain develops very rapidly during the last trimester of pregnancy, the brain of infants who are born preterm is very vulnerable to changes in oxygen and nutrient supply in the neonatal period.Brain cells need a sufficient amount of oxygen for function, growth, and development. Cerebral O 2 supply is determined by the arterial oxygen content (CaO 2 ) and cerebral blood flow (CBF). If cerebral autoregulation is impaired, then hypotension results in low CBF and leads to decreases in cerebral O 2 supply. When cerebral O 2 supply becomes insufficient to meet the cellular demand for oxygen, a sequence of events will be triggered, eventually leading to neonatal brain cell dysfunction or damage.EEG features provide information on brain cell function (2). Energy failure in the brain, e.g. as a result of reduced cerebral O 2 supply during hemorrhagic hypotension, leads to a blockade of neuronal synaptic function and reduced electrical firing of neurons. A disadvantage of conventional EEG is that it requires the presence of an expert to interpret the large volumes of data. In an effort to solve this problem, various methods of compressing the EEG signal have been developed, the cerebral function monitor (CFM) being one of them. CFM correlates well with conventional multichannel EEG evaluation of cortical neuronal activity in neonates, except for the recognition of very short seizure activity patterns (3-8). Noninvasive recording of electrocortical brain activity (ECBA) by means of CFM-like signals can be used as a measure for brain cell function in the newborn period (2). Abnormal tracings are indicative of the risk for neonatal death and in the survivors to neurodevelopmental outcome (3,9 -12).

Cerebral Cortical Tissue Damage After Hemorrhagic Hypotension in Near-Term Born Lambs

“…As expected, low glutamate, aspartate, and cGMP concentrations were found in the CSF of the siblings as well as an optimal MAP2 staining. The values of cerebral O 2 supply, cerebral O 2 consumption, and ECBA during normotension in this study were comparable to values reported previously (7,8,13). Furthermore, the effect of delivery on the physiologic and biochemical parameters is assumed to be negligible after a cesarean section, in particular after a stabilization period of 3 h.…”

“…To obtain hypotension, blood was withdrawn in a stepwise manner until MABP had dropped to approximately 30% of normotension (13). The blood withdrawal procedure lasted approximately 15-20 min.…”

“…In a previous study, we demonstrated in near-term lambs that brain cell function deteriorated during hypotension when MABP had been reduced to 30% of normotension (13). The aim of the present study is to elucidate 1) to what extent the functional disturbance of the cerebral cortex, as measured with ECBA, is related to cerebral cortical tissue damage, as estimated by MAP2 staining after 2.5 h of hemorrhagic hypotension in lambs born at 131 d of gestation, and 2) whether there is a relationship between the glutamate, NO, cGMP pathway, and the development of cerebral cortical tissue damage.…”

Purine and Pyrimidine Metabolism and Electrocortical Brain Activity during Hypotension in Near-Term Lambs

“…Per step, approximately 25 ml/kg were removed in order to reach a 5-to 10-mm Hg MABP reduction, until MABP had dropped to approximately 30% of baseline [17] . The total hypotensive period lasted 2.5 h. Thereafter, mean values of MABP, Q car and ECBA were calculated over 3 min and cerebral arterial and venous blood samples were obtained for blood gas analysis to calculate cerebral O 2 supply and O 2 consumption.…”

“…The effect of hemorrhagic hypotension on brain cell function in the near-term born lamb has been elucidated in a previous study [17] . Furthermore, the relationship between brain cell energy shortage after hypoxemia, as measured by purine and pyrimidine metabolism, and brain cell function, as measured by ECBA, after nearterm birth was established [18] .…”