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Background: Insufficient cerebral O2 supply leads to cellular energy failure and loss of brain cell function. The relationship between the severity of cellular energy failure due to hemorrhagic hypotension and the loss of electrocortical brain activity (ECBA), as a measure of brain cell function, is not yet fully elucidated in near-term born lambs., Objectives: To study the relationship between cerebral purine and pyrimidine metabolism, as a measure of brain cell energy failure, and brain cell function after hemorrhagic hypotension in near-term born lambs., Methods: Eight near-term lambs (term 147 days) were delivered at 131 days of gestation. After a stabilization period, mean arterial blood pressure was reduced till 30% of baseline by withdrawal of blood. Cerebrospinal fluid (CSF) was obtained at the end of the hypotensive period (2.5 h). CSF from 8 siblings was used for comparison. HPLC was used to determine purine and pyrimidine metabolites in CSF, as a measure of cellular energy failure. ECBA was calculated as the root mean square value of a band-filtered (2-16 Hz) one-channel EEG., Results: Values of guanosine, inosine, hypoxanthine, xanthine and uridine were significantly higher, while ECBA was significantly lower after hemorrhagic hypotension than control values. The concentrations of inosine, hypoxanthine, xanthine and uridine were significantly negatively linearly related to ECBA., Conclusions: Brain cell function is negatively related to concentrations of inosine, hypoxanthine, xanthine and uridine in the CSF after hemorrhagic hypotension in near-term born lambs., (Copyright (c) 2006 S. Karger AG, Basel.)

The influence of skin on the bias and reproducibility of regional cerebral oxygenation measurements is investigated using cw near-infrared spectroscopy (NIRS). Receiving optodes are placed over the left and right hemispheres of a piglet (C3, C4 EEG placement code) and one transmitting optode centrally (Cz position). Optical densities (OD) are measured during stable normo, mild, and deep hypoxemia. This is done for skin condition 1: all optodes on the skin; skin condition 2: transmitting optode on the skin and one receiving optode on the skull; and skin condition 3: all optodes on the skull. Absolute changes of oxy- (cO2Hb), deoxyhemoglobin (cHHb), and total hemoglobin (ctHb) concentrations [micromolL] are calculated from the ODs. These absolute changes are calculated for each skin condition with respect to normoxic condition. Additionally, for skin condition 2, the difference of concentration changes between receiver 1 (skull) and receiver 2 (skin) is calculated. The effect of skin removal is an average increase of attenuation changes by a factor of 1.66 (=0.51 OD) and of the concentration changes due to the arterial oxygen saturation steps by 23%. We conclude that skin significantly influences regional oxygenation measurements. Nevertheless, it is hypothesized that the estimated concentration changes are dominated by changes of the oxygenation in the brain.

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 O2 supply threshold level for preservation of brain function during hypotension in near-term-born lambs. Lambs were delivered at 141 or 127 d of gestation. Hypotension was induced by stepwise withdrawal of blood. Mean arterial blood pressure (MABP) baseline levels were 63.2 (6.4) in 141-d and 54.4 (15.5) mm Hg in 127-d lambs. The MABP threshold below which MABP and blood flow in the left carotid artery were linearly related was 36.1 (13.1) mm Hg in 141-d lambs. In 127-d lambs, MABP and blood flow in the left carotid artery were linearly related over the whole range of recorded MABP values. Electrocortical brain activity (ECBA) was used as a measure of brain function. Thresholds of MABP for maintenance of ECBA were reached at, respectively, 31.6% (4.9%) of baseline in 141-d and 61.9% (13.0%) of baseline MABP in 127-d lambs. However, thresholds of cerebral O2 supply for maintenance of ECBA were similar in both GA groups. We conclude that thresholds of cerebral O2 supply for maintenance of brain cell function are independent of GA but are reached at higher MABP levels in 127-d than in 141-d lambs and therefore places the sick preterm infant easily at risk for ischemic cerebral injury.

Background: Sufficient O2 supply to the brain is necessary for adequate cerebral energy metabolism, function and growth., Objectives: To elucidate the relation between changes in cerebral arterial O2 content and cerebral O2 supply and changes in the oxygenation state of cerebral hemoglobin, and to determine whether concentration changes in oxyhemoglobin (DeltacO2Hb), deoxyhemoglobin (DeltacHHb), and cerebral arterial oxygenation (DeltacHbD; the difference between DeltacO2Hb and DeltacHHb), and cerebral blood volume (DeltaCBV) can be used to assess the decline in brain cell function during hypoxemia in lambs born near term., Methods: 17 preterm lambs were delivered at a mean gestational age of 133 days. Decreases in cerebral arterial oxygen content were induced by a stepwise reduction in inspired oxygen concentration. Mean values of all continuous variables were calculated over the last 180 s of each hypoxemic level. Cerebral arterial blood gases were analyzed at the end of each level to calculate cerebral arterial O2 content and cerebral O2 supply., Results: Changes in cerebral arterial O2 content and cerebral O2 supply were positively linearly related with DeltacO2Hb and DeltacHbD, and negatively with DeltacHHb and the concentration changes in total hemoglobin. Electrocortical brain activity remained stable until the cO2Hb and cHbD decreased to >3.0 +/- 0.9 and >8.1 +/- 1.9 (mean +/- SD) micromol/100 g, respectively, and cHHb and CBV increased to >4.3 +/- 1.7 and 1.37 +/- 0.48 ml/100 g, respectively, as compared to baseline., Conclusions: Changes in cerebral arterial O2 content and cerebral O2 supply are adequately reflected by changes in the oxygenation state of cerebral hemoglobin. Concentration changes in DeltacO2Hb, DeltacHHb, DeltacHbD and DeltaCBV can be used to assess the decline in brain cell function during hypoxemia in lambs born near term., (Copyright (c) 2005 S. Karger AG, Basel.)

Insufficient cerebral O(2) supply leads to brain cell damage and loss of brain cell function. The relationship between the severity of hypoxemic brain cell damage and the loss of electrocortical brain activity (ECBA), as measure of brain cell function, is not yet fully elucidated in near-term newborns. We hypothesized that there is a strong relationship between cerebral purine and pyrimidine metabolism, as measures of brain cell damage, and brain cell function during hypoxemia. Nine near-term lambs (term, 147 d) were delivered at 131 (range, 120-141) d of gestation. After a stabilization period, prolonged hypoxemia (fraction of inspired oxygen, 0.10; duration, 2.5 h) was induced. Mean values of carotid artery blood flow, as a measure of cerebral blood flow, and ECBA were calculated over the last 3 min of hypoxemia. At the end of the hypoxemic period, cerebral arterial and venous blood gases were determined and CSF was obtained. CSF from 11 normoxemic siblings was used for baseline values. HPLC was used to determine purine and pyrimidine metabolites in CSF, as measures of brain cell damage. Concentrations of purine and pyrimidine metabolites were significantly higher in hypoxemic lambs than in their siblings, whereas ECBA was lower in hypoxemic lambs. Significant negative linear relationships were found between purine and pyrimidine metabolite concentrations and, respectively, cerebral O(2) supply, cerebral O(2) consumption, and ECBA. We conclude that brain cell function is related to concentrations of purine and pyrimidine metabolites in the CSF. Reduction of ECBA indeed reflects the measure of brain damage due to hypoxemia in near-term newborn lambs.

Adequate cerebral perfusion is necessary to preserve cerebral O(2) supply in order to maintain brain cell function. Our aim was to assess the influence of gestational age on the response of cerebral hemodynamics to hypoxemia and to determine thresholds of cerebral O(2) supply for preservation of brain cell function in preterm born lambs. Lambs were delivered by hysterotomy at 141 (n=5), 134 (n=5) or 127 (n=7) days of gestation. Decreases in arterial oxygen content (CaO(2)) were induced by stepwise reduction of the fraction of O(2) in inspired air (FiO(2)). Mean arterial blood pressure (MABP), carotid artery blood flow (Qcar), and electrocortical brain activity as a measure of brain cell function, were continuously recorded. Cerebral arterial blood gases were analyzed at the end of each hypoxemic level to calculate CaO(2) and cerebral O(2) supply. In contrast to 141-day lambs, MABP could not be maintained in 134-day and 127-day lambs at levels of severe hypoxemia. Increases in Qcar were observed at levels of moderate hypoxemia in all gestational age-groups. Albeit Qcar increased further at levels of severe hypoxemia in the 141-day lambs, Qcar declined under these conditions in the 134-day and 127-day lambs. The threshold of cerebral O(2) supply for the preservation of brain cell function was however similar in all gestational age-groups (1.7 ml/min). It is concluded that the ability to maintain cerebral function during hypoxemia depends upon the ability to preserve cerebral O(2) supply by means of cerebral hemodynamic compensatory mechanisms, which are not fully matured until 96% of gestation.

Abstract: Sufficient O2-supply to the brain is necessary for an adequate cerebral energy metabolism, function and growth. To elucidate the relation between changes in, respectively, mean arterial blood pressure (MABP) and cerebral O2-supply and changes in the oxygenation state of hemoglobin during hypotension in preterm born lambs. Preterm lambs were delivered at 141 days (n=7) or 127 days (n=7) of gestation. Hypotension was induced by stepwise withdrawal of blood. Cerebral arterial blood gases were analyzed at the end of each level to calculate cerebral O2-supply. Near-infrared spectroscopy was used to measure changes in the concentration of cerebral oxyhemoglobin (cO2Hb), deoxyhemoglobin (cHHb) and cHbD (the difference between cO2Hb and cHHb). In the 141 and the 127 d lambs, changes in MABP and cerebral O2-supply were positively linearly related with ΔcO2Hb, and negatively with ΔcHHb. MABP was positively linearly related with changes in cHbD. During hemorrhagic hypotension, changes in MABP and cerebral O2-supply are reflected by changes in the oxygenation state of cerebral hemoglobin in near-term born lambs. [Copyright &y& Elsevier]