Biomedical subjects

M Delivoria-Papadopoulos

Publications and source records attributed to M Delivoria-Papadopoulos.

At least 19 recordsLinked to original sources

PubMed1995

Neuroprotective effect of phenytoin against in utero hypoxic brain injury in fetal guinea pigs.

The present study tests the hypothesis that phenytoin, an antiepileptic agent known to block Na+ and Ca2+ channels, will prevent hypoxic brain injury in the fetus by preventing lipid peroxidation and preserving Na+,K(+)-ATPase activity. Studies were performed in 37 fetuses obtained from pregnant guinea pigs at 58-60 days gestation (term). The pregnant guinea pigs were divided into four groups: a normoxic group, a hypoxic group, a normoxic group treated with phenytoin, and a phenytoin treated hypoxic group. There were eight to ten fetal guinea pigs in each group. The treatment groups were given phenytoin 30 mg/kg (50 mg phenytoin/ml solvent) intraperitoneally. Hypoxia was induced by exposing the guinea pigs to 7% oxygen for 60 min. This level of hypoxia has been shown to decrease ATP and phosphocreatine levels by 90%. The fetal brains were harvested and the brain cell membranes were prepared from each group of fetuses. Na+,K(+)-ATPase activity and lipid peroxidation products, measured as relative fluorescent intensity, were determined. The mean Na+,K(+)-ATPase activity in the control, hypoxic, phenytoin-normoxic and phenytoin-hypoxic groups was 56.4 +/- 9.7, 37.9 +/- 10.6, 47.0 +/- 8.4 and 52.0 +/- 9.7 mumol inorganic phosphate/mg protein per h, respectively. The hypoxic group had significantly less Na+,K(+)-ATPase activity than both the normoxic group (P < 0.01), and the phenytoin treated hypoxic group (P < 0.05). There was no significant difference between the normoxic group and either of the phenytoin-treated groups (P = ns).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Effect of in utero hypoxia on the ouabain/strophanthidin binding site of the fetal guinea pig brain cell membrane Na+,K(+)-ATPase.

This study investigates the effect of hypoxia on the high affinity strophanthidin/ouabain binding site of brain cell membrane Na+,K(+)-ATPase in 30, 45 and 60 day (term) fetal guinea pigs. Studies were performed on 30 fetuses randomized to either normoxic or hypoxic conditions. The hypoxic fetuses were exposed to maternal hypoxia (FiO2 = 7%) for 60 min. Brain cell membrane fractions were prepared, and the rate of ATP hydrolysis was determined at varying concentrations of strophanthidin. In every experiment with 45 and 60 day brain preparations hypoxia caused a leftward shift in the IC50, but this did not reach the level of statistical significance (4.0 x 10(-5) normoxic, 9.0 x 10(-6) hypoxic, P = 0.069, at 45 days; 9.5 x 10(-6) M normoxic, 8.5 x 10(-6) M hypoxic, P = 0.23, at 60 days). If hypoxia does cause a true left shift this would indicate greater sensitivity of the hypoxic brain to inhibitor. In addition, [3H]ouabain binding studies were performed. In the 30 day normoxic brain preparations, the Kd was 24.7 +/- 5.6 nM, and the Bmax was 0.26 +/- 0.08 pmol/mg protein. At 45 days the ouabain binding sites showed no change in affinity following hypoxia (Kd = 14.6 +/- 1.7 nM normoxic, 13.0 +/- 0.8 nM hypoxic, P = NS); however, there was a significant decrease in receptor number following hypoxia (Bmax = 22.1 +/- 2.2 pmol/mg protein normoxic, 16.9 +/- 0.3 pmol/mg protein hypoxic, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

The effect of acute hypoglycemia on the cerebral NMDA receptor in newborn piglets.

The effects of acute insulin-induced hypoglycemia on the cerebral NMDA receptor in the newborn were examined by determining [3H]MK-801 binding as an index of NMDA receptor function in 6 control and 7 hypoglycemic piglets. In hypoglycemic animals, the glucose clamp technique with constant insulin infusion was used to maintain a blood glucose concentration of 1.2 mmol/l for 120 min before obtaining cerebral cortex for further analysis; controls received a saline infusion. Concentrations of glucose, lactate, ATP, and PCr were measured in cortex, and Na+,K(+)-ATPase activity was determined in a brain cell membrane preparation. [3H]MK-801 binding was evaluated by: (1) saturation binding assays over the range of 0.5-50 nM [3H]MK-801 in the presence of 100 microM glutamate and glycine; and (2) binding assays at 10 nM [3H]MK-801 in the presence of glutamate and/or glycine at 0, 10, or 100 microM. Blood and brain glucose concentrations were significantly lower in hypoglycemic animals than controls. There was no change in brain ATP with hypoglycemia, but PCr was decreased 80% compared to control (P < 0.05). Na+,K(+)-ATPase activity was 13% lower in hypoglycemic animals (P < 0.05). Based on saturation binding data, hypoglycemia had no effect on the number of functional receptors (Bmax), but the apparent affinity was significantly increased, as indicated by a decrease in the Kd (dissociation constant) from the control value of 8.1 +/- 1.6 nM to 5.5 +/- 2.1 nM (P < 0.05). Augmentation of [3H]MK-801 binding by glutamate and glycine alone or in combination was also significantly greater in the hypoglycemic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1995

Transcranial optical path length in infants by near-infrared phase-shift spectroscopy.

BACKGROUND: Near-infrared spectroscopy (NIRS) is an emerging technique for noninvasive, bedside monitoring of cerebral oxygenation and blood flow. Traditionally, it has relied on the Beer's Law relationship in which the concentration of light-absorbing oxygen-carrying pigments is proportional to their light absorbance, and inversely proportional to an optical path length (a measure of the distance traveled by photons passing through the tissue). In practice, NIRS has been based upon assumptions that mean transcranial optical path length, the average optical path length for a given patient, is constant among patients and independent of the wavelength of light used. OBJECTIVE: The objective of our study was to measure mean optical transcranial path length in infants as a step in allowing quantitation of cerebral oxygenation. METHODS: We measured mean transcranial optical path length in 34 infants, aged 1 day to 3 years, using amplitude-modulated phase-shift spectroscopy at 754 nm and 816 nm. Optical transcranial path lengths (mean +/- SEM) were 8.6 +/- 0.9 cm, 11.1 +/- 0.9 cm, and 11.3 +/- 0.9 cm at 754 nm, and 8.8 +/- 0.9 cm, 11.2 +/- 0.8 cm, and 11.1 +/- 0.9 cm at 816 nm, using emitter-detector separations of 1.8, 2.5, and 3.0 cm, respectively. Optical path length increased as emitter-detector separation, head circumference, or age increased. Variance in the ratio of mean optical path lengths at the two different wavelengths exceeded that accounted for by variation in repeated measures alone (p < 0.001), suggesting that optical path length is also not independent of wavelength. CONCLUSIONS: NIRS instrument emitter-detector geometry, subject age, head size, and wavelength used each influence optical path length. Quantitative NIRS measurements in clinical use may require concurrent measurement of both absorbance and optical path length at each wavelength, or use of newer measures that are not based upon Beer's Law assumptions.

Child, Preschool↗

PubMed1995

Comparison of postasphyxial resuscitation with 100% and 21% oxygen on cortical oxygen pressure and striatal dopamine metabolism in newborn piglets.

The present study tests the hypothesis that ventilation with 100% O2 during recovery from asphyxia leads to greater disturbance in brain function, as measured by dopamine metabolism, than does ventilation with 21% oxygen. This hypothesis was tested using mechanically ventilated, anesthetized newborn piglets as an animal model. Cortical oxygen pressure was measured by the oxygen-dependent quenching of phosphorescence, striatal blood flow by laser Doppler, and the extra-cellular levels of dopamine and its metabolites by in vivo microdialysis. After establishment of a baseline, both the fraction of inspired oxygen (FiO2) and the ventilator rate were reduced in a stepwise fashion every 20 min over a 1-h period. For the subsequent 2-h recovery, the animals were randomized to breathing 21 or 100% oxygen. It was observed that during asphyxia cortical oxygen pressure decreased from 36 to 7 torr, extracellular dopamine increased 8,300%, and dihydroxyphenylacetic acid and homovanillic acid decreased by 65 and 60%, respectively, compared with controls. During reoxygenation after asphyxia, cortical oxygen pressure was significantly higher in the piglets ventilated with 100% oxygen than in those ventilated with 21% oxygen (19 vs. 11 torr). During the first hour of reoxygenation, extracellular dopamine levels decreased to approximately 200% of control in the 21% oxygen group, whereas these levels were still much higher in the 100% oxygen group (approximately 500% of control). After approximately 2 h of reoxygenation, there was a secondary increase in extracellular dopamine to approximately 750 and approximately 3,000% of baseline for the animals ventilated with 21 and 100%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Effect of nordihydroguaiaretic acid on cerebral blood flow and metabolism during hypoxia in newborn piglets.

Nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, was investigated for its effect on cerebral blood flow (CBF) and cortical oxygen consumption during hypoxia in 9 anesthetized, ventilated newborn piglets. CBF was measured by radioactive microspheres while brain cortical metabolism was evaluated by continuous 31P-NMR spectroscopy. Five piglets were treated with NDGA (3 mg/kg i.v. in 50% ethanol as vehicle) prior to hypoxia and had CBF measured before NDGA (control), 15 min after NDGA (baseline) and then after 15 and 45 min of hypoxia following NDGA. Another 4 piglets were treated with vehicle (2 ml/kg 50% ethanol) under the same protocol. In the NDGA-treated piglets, cerebral cortical O2 consumption for a given PCr/Pi was significantly increased (p < 0.05) compared to non-NDGA. Since NDGA inhibits production of vasoconstricting leukotrienes during hypoxia, cortical capillary beds otherwise constricted may be perfused following NDGA, thus increasing the O2-consuming tissue area.

Animals↗

PubMed1995

Brain cell membrane function during hypoxia in hyperglycemic newborn piglets.

To test the hypothesis that acute hyperglycemia reduces changes in cell membrane structure and function during cerebral hypoxia in the newborn, brain cell membrane Na+,K(+)-ATPase activity and levels of membrane lipid peroxidation products were measured in four groups of anesthetized, ventilated newborn piglets: normoglycemia/normoxia (control, group 1, n = 12), hyperglycemia/normoxia (group 2, n = 6), untreated hypoxia (group 3, n = 10), and hyperglycemia/hypoxia (group 4, n = 7). Hyperglycemia (blood glucose concentration 20 mmol/L) was induced using the glucose clamp technique. The hyperglycemic glucose clamp was maintained for 90 min before onset of hypoxia and throughout the period of hypoxia. Cerebral tissue hypoxia was induced in groups 3 and 4 by reducing fraction of inspired oxygen for 60 min and was documented by a decrease in the ratio of phosphocreatine to inorganic phosphate as measured using 31P-nuclear magnetic resonance spectroscopy. Blood glucose concentration during hypoxia in hyperglycemic hypoxic animals was 20.7 +/- 1.2 mmol/L, compared with 10.3 +/- 1.7 mmol/L in untreated hypoxic piglets (p < 0.05). Peak blood lactate concentrations were not significantly different between the two hypoxic groups (8.4 +/- 2.8 mmol/L versus 7.8 +/- 1.6 mmol/L). In cerebral cortical membranes prepared from the untreated animals, cerebral tissue hypoxia caused a 25% reduction in Na+,K(+)-ATPase activity compared with normoxic controls and an increase in conjugated dienes and fluorescent compounds, markers of lipid peroxidation. In contrast, Na+,K(+)-ATPase activity and levels of lipid peroxidation products in hyperglycemic hypoxic animals were not significantly different from the values in control normoxic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1994

Effect of hemorrhagic hypotension on extracellular level of dopamine, cortical oxygen pressure and blood flow in brain of newborn piglets.

The present study describes the relationships between extracellular striatal dopamine, cortical oxygen pressure and blood flow in brain of newborn piglets during hemorrhagic hypotension. Cerebral oxygen pressure was measured optically by the oxygen dependent quenching of phosphorescence; extracellular dopamine by in vivo microdialysis; striatal blood flow was monitored by a laser Doppler. Following a 2 h stabilization period after implanting the microdialysis and laser Doppler probes in the striatum, the mean arterial blood pressure (MABP) was decreased in stepwise manner from 87 +/- 4 Torr (control) to 35 +/- 5 Torr, during 63 min. The whole blood was then reinfused and measurements were continued for 45 min. Statistically significant decrease in blood flow, 10%, was observed when arterial blood pressure decreased to about 53 Torr. With further decrease blood pressure to 35 Torr, blood flow decreased to about 35% of control (P < 0.01). Cortical oxygen pressure decreased almost proportional to decrease in blood pressure. The progressive decrease in MABP from 87 +/- 4 Torr to 65 +/- 6, 52 +/- 7, and 35 +/- 5 Torr resulted in cortical oxygen pressure decreasing from 45 +/- 4 Torr to 33 +/- 3 Torr (P < 0.05), 24 +/- 4 Torr (P < 0.01) and 13 +/- 3 Torr (P < 0.01). The levels of extracellular dopamine in the striatum increased with decreasing cortical oxygen pressure. As cortical oxygen decreased, the extracellular dopamine increased to 230%, 420% and 3200% of control, respectively. Our results show that in mild hypotension total blood flow is well maintained but oxygen pressure in the microvasculature decreases, possibly due to heterogeneity in the regulatory mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Effect of cyclooxygenase inhibition on brain cell membrane lipid peroxidation during hypoxia in newborn piglets.

To test the hypothesis that indomethacin, an inhibitor of cyclooxygenase, reduces free radical-induced brain cell membrane changes during cerebral hypoxia, we determined levels of brain cell membrane lipid peroxidation products and Na+,K(+)-ATPase activity as indicators of free radical production and membrane function, respectively, in 29 newborn piglets divided into 4 groups. Eight saline- and 4 indomethacin-treated normoxic animals served as controls; 8 saline-pretreated piglets and 9 piglets pretreated with indomethacin were exposed to hypoxic hypoxia for 60 min. Cerebral hypoxia was documented using 31P-NMR spectroscopy. In saline-pretreated hypoxic animals Na+,K(+)-ATPase activity decreased significantly and levels of membrane lipid peroxidation products increased significantly compared to normoxic controls. Indomethacin pretreatment prevented the hypoxia-induced increase in membrane lipid peroxidation products but had no effect on the decrease in Na+,K(+)-ATPase activity. Thus the apparent reduction in free radical production by indomethacin pretreatment did not prevent the hypoxia-induced change in Na+,K(+)-ATPase activity.

Animals↗

PubMed1994

Proton MR spectroscopy of brain abnormalities in neonates born to HIV-positive mothers.

PURPOSE: To examine the sensitivity of proton MR spectroscopy for detecting early central nervous system abnormalities in neonates born to human immunodeficiency virus (HIV)-positive mothers. METHODS: Asleep, unsedated, and continuously monitored by electrocardiography, 10 newborns, 5 with HIV-positive and 5 with HIV-negative mothers, were studied within the first 10 days of life in a 1.5-T scanner. After T1- and T2-weighted images were obtained, proton spectra were performed using voxels of interest (3.4 cm3) in the deep parietooccipital white matter. Peaks were identified as N-acetyl-aspartate (2.0 ppm), creatine and phosphocreatine (3.0 ppm), choline (3.2 ppm), and inositol (3.5 ppm). Peak areas were used to calculate metabolic ratios: N-acetyl-aspartate to creatine, inositol to creatine, and creatine to choline. RESULTS: All newborns of HIV-positive mothers had abnormal proton spectra compared with control infants; a nonspecific amino acid peak in the 2.1- to 2.6-ppm area was elevated, broad, and overlapping the N-acetyl-aspartate peak in all the HIV-exposed newborns and in only 1 of the 5 control newborns. The choline-to-creatine ratio was higher in HIV-exposed newborns at 2.3 +/- 0.4 (normal term, 0.9 +/- 0.3), as was the N-acetyl-aspartate-to-creatine ratio at 2.6 +/- 0.9 (for control subjects, 1.2 +/- 0.4). MR images from these brain regions were all considered normal. Because acquired immunodeficiency syndrome develops in only a small fraction of neonates born to HIV-seropositive mothers, the above spectral abnormalities found in all our subjects may result from indirect effects of HIV, such as intrauterine growth retardation. CONCLUSIONS: These findings indicate that proton MR spectroscopy might play an important role in detecting early central nervous system complications in newborns of HIV-seropositive mothers.

AIDS Dementia Complex↗

PubMed1993

Effects of graded levels of tissue oxygen pressure on dopamine metabolism in the striatum of newborn piglets.

The effect of graded levels of tissue hypoxia on the extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid has been monitored in vivo by microdialysis. Reproducible levels of decreased oxygen in the brain were obtained by increasing the rate of ventilation from the control value of 25/min to as high as 95/min. With increasing ventilatory rate, the oxygen pressure in the cortex decreased from approximately 40 torr to 16 torr. As the oxygen pressure decreased stepwise from 40 to 27, 22, and 16 torr, the dopamine levels in the extracellular medium rose by 70, 90, and 150%, respectively, returning to baseline within a few minutes of return to control ventilation rates. Levels of the catabolic products 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid decreased with decreasing tissue oxygen. Unlike the dopamine levels, these catabolite levels continued to decrease through 30 min of recovery (to 50% of control), returning to baseline only after recovery periods of 1-2 h. These data suggest that hypoxia induces long-term alterations in the neurotransmitter turnover. The marked effects of mild tissue hypoxia (decrease of oxygen from 40 torr to 26 torr) on both the extracellular dopamine concentration and dopamine metabolism indicate that the metabolic consequences of decreased tissue oxygen pressure extend to higher values than generally appreciated.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Adaptive control of inspired oxygen delivery to the neonate.

Adaptive adjustment of inspired oxygen (FIO2), based on a desired percent arterial hemoglobin saturation (SO2) was achieved by on-line bedside control of the oxygen concentration delivered to the neonate. Fourteen infants with bronchopulmonary dysplasia (BW, 860 +/- 80 g; GA, 26 +/- 1 weeks; study age, 41 +/- 8 days) receiving oxygen-air mixtures by hood were studied. The desired range of SO2 from 92 to 96% with a target value of 95% was determined by pulse oximetry and maintained with adjustment of FIO2 using three modes: 1) standard neonatal intensive care protocol with oxygen delivery evaluated at 20 minutes intervals; 2) bedside manual control with FIO2 manipulation every 2 to 5 minutes; and 3) adaptive control with on-line adjustment of FIO2 according to a specifically designed adaptive program. Each study period was of 40 minute duration. SO2 values within a steady 94 to 96% range was achieved for 54% of the time with standard protocol, compared to 69% (P less than 0.01) with bedside manual control and 81% (P less than 0.01) with adaptive control. In addition, fluctuations in SO2 values and overshoots were less apparent with adaptive control of oxygen delivery. These data describe adaptive FIO2 control as an efficient alternative technique for achieving a stable desired range of oxygenation in neonates.

Bronchopulmonary Dysplasia↗

PubMed1992

Effect of hyperventilation on oxygenation of the brain cortex of neonates.

A new phosphorescence imaging method (Rumsey et al, Science (1988) 1649) has been used to continuously monitor the oxygen pressure in the blood of the cerebral cortex of newborn pigs. The animals' blood pressure was continuously measured and PaCO2, PaO2 and arterial blood pH were measured periodically. The oxygen pressure in the blood was quantitatively determined for regions of about 100 um square within the image (from a total field of about 3 mm diameter). It was observed that during hyperventilation, which lowered PaCO2 and increased pH of the blood, oxygen pressure decreased in proportion to the decrease in PaCO2. For example, hyperventilation which decreased PaCO2 from its normal value of 40 Torr to 10 Torr caused a rapid (within 5 minutes) decrease in oxygen pressure in the blood of capillaries and veins to approximately 1/4 of normal.

Animals↗

PubMed1992

NMDA receptor modification in the fetal guinea pig brain during hypoxia.

The effect of maternal hypoxia on the modification of the fetal brain cell membrane N-methyl-D-aspartate (NMDA) receptor and its modulatory sites was investigated. Experiments were conducted in pregnant guinea pigs of 60 days of gestation. Guinea pig fetuses were exposed to maternal hypoxia (FiO2 = 7%) for 60 minutes. Tissue hypoxia in the fetal brain was documented biochemically by decreased levels of ATP and phosphocreatine (91.3% and 88.6% lower than normoxia, respectively). MK-801 binding characteristics (Bmax = number of receptors, Kd = affinity of receptor) were used as an index of NMDA receptor modification. P2 membrane fraction was prepared from the cortex of normoxic and hypoxic fetal brain and washed thoroughly before carrying out the binding assay. In hypoxic brains, Bmax decreased from the normoxic control level 0.79 +/- 0.03 pmol/mg protein to 0.58 +/- 0.03 pmol/mg protein (P < 0.005) and Kd value decreased (increased affinity) from 8.54 +/- 0.27 nM to 4.01 +/- 0.23 nM (P < 0.005) respectively. The MK-801 binding in the absence of added glutamate and glycine in hypoxic brain was 100% higher as compared to controls, indicating an increased sensitivity of the NMDA receptor to activation. The spermine dependent maximum activation of the NMDA receptor increased to 44% in the hypoxic animals as compared to 25% in controls. The Mg2+ response of the NMDA receptor was not affected by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Modification of modulatory sites of NMDA receptor in the fetal guinea pig brain during development.

Ontogeny of the NMDA receptor and modification of its modulatory sites in the developing fetus brain was determined. MK-801 binding characteristics in the presence of glycine, glutamate, Mg2+ and spermine were determined and used as an index of NMDA receptor modification. Experiments were performed on guinea pig fetuses at 30, 45, 50, 55, and 60 days (term = 63 days) of gestation. The Bmax value increased approximately three-fold from 30 days to 60 days of gestation. The Kd value decreased during the 45-50 day period and then increased toward the end of gestation. The Bmax value reached its maximum level by 55 days of gestation, indicating the presence of a maximum number of NMDA receptors by this age, while the apparent affinity of the receptor showed its peak at 45-50 days of gestation, indicating a potential role for NMDA receptor during the proliferation period of brain development in the guinea pig fetus. The activation of NMDA receptor in the presence of glutamate (10 microM) and glycine (10 microM), as measured by MK-801 binding, was absent at 30 days gestation, with the earliest observation occurring at 35 days gestation. The spermine dependent activation decreased with gestational age. Mg2+ ions increased MK-801 binding in the range of 1-20 microM concentration. Sensitivity to Mg2+ dependent activation increased with the gestational age (from 10 microM Mg2+ at 45 days to 2.5 microM at 55 and 60 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Fluctuations in cerebral oxygenation and blood volume during endotracheal suctioning in premature infants.

To investigate the effect that suctioning of the endotracheal tube has on the cerebral circulation, we monitored brain intravascular hemoglobin saturation (tHbo2%), cerebral blood volume (CBV), and arterial hemoglobin saturation (Spo2) during suctioning in 12 infants (24 to 33 weeks of gestational age) with respiratory distress syndrome treated with mechanical ventilation. The tHbo2% and CBV values were monitored over the forebrain by dual-wavelength near-infrared spectroscopy, and Spo2 was monitored by pulse oximetry of a finger. The monitored variables were stable during the baseline period. With suctioning, Spo2 decreased from 94% +/- 1% to 84% +/- 1%, tHbo2% decreased, and CBV increased (p less than 0.05). Desaturation in the arterial and cerebral circulations began within 5 seconds of the onset of suctioning. Arterial reoxygenation began with the onset of reventilation, whereas reoxygenation in the brain was delayed by 15 seconds. The Spo2, tHbo2%, and CBV values returned to baseline within 1 minute of reventilation. Studies were repeated in six of the infants after the fraction of inspired oxygen was increased to attain a baseline Spo2 of 100%. In the preoxygenated infants, tHbo2%, CBV, and Spo2 remained constant during suctioning. These studies confirm that endotracheal suctioning results in transient hypoxemia, and demonstrate that this is reflected in the brain by vasodilation and deoxygenation. These effects are preventable by preoxygenation before suctioning.

Brain↗

PubMed1992

Kinetics of cerebral deoxygenation during deep hypothermic circulatory arrest in neonates.

Brain injury associated with neonatal congenital heart operations performed during deep hypothermia and/or total circulatory arrest is often attributed to cerebral hypoxia. We studied the kinetic changes in cerebrovascular hemoglobin O2 saturation (HbO2%) and total hemoglobin concentration (Hbtotal) in 17 neonates undergoing cardiac surgery as they were cooled to 15 degrees C, underwent total circulatory arrest, and were rewarmed. HbO2% and Hbtotal in brain vasculature were monitored noninvasively by near-infrared spectroscopy. Neonates were cooled over 12 min and rewarmed over 15 min while being perfused using cardiopulmonary bypass (CPB). Total circulatory arrest lasted from 20 to 70 min. We found that HbO2% in brain vasculature increased during the initial 8 min of CPB as nasopharyngeal temperature decreased, and then remained constant until circulatory arrest. After the onset of circulatory arrest, cerebrovascular HbO2% decreased curvilinearly for 40 min; no further hemoglobin desaturation was observed from 40 to 70 min of arrest. The changes in cerebrovascular Hbtotal were quite different from those in HbO2%, as Hbtotal decreased during the initial minute of CPB and circulatory arrest and then remained constant until recirculation. Brain intravascular HbO2% and Hbtotal increased within 3 min after the onset of recirculation to prearrest levels, and during rewarming, HbO2% decreased to normothermic baseline values. The results demonstrate that cerebral oxygenation increased during CPB cooling; O2 was consumed by the neonatal brain during the initial 40 min of deep hypothermic circulatory arrest; and cerebral oxygenation was restored on recirculation. These observations may be important in identifying the etiologies of brain injury during neonatal congenital heart surgery.

Brain↗

PubMed1992

Effect of graded hypoxia on brain cell membrane injury in newborn piglets.

Alterations in brain cell membrane structure and function during cerebral hypoxia were investigated by measuring Na+,K(+)-ATPase activity and levels of lipid peroxidation products in brain cell membranes obtained from newborn piglets following exposure to 60 min of hypoxic hypoxia in vivo. Cerebral hypoxia was documented as a decrease in the ratio of phosphocreatine to inorganic phosphate (PCr/Pi) using 31P-NMR spectroscopy. During hypoxia (FiO2 0.07-0.11), PCr/Pi decreased 28-47% compared to the corresponding baseline value without a decrease in cerebral ATP levels. No change in brain cell membrane Na+,K(+)-ATPase activity was observed for changes in PCr/Pi of less than 30%. When PCr/Pi was at least 30% lower than baseline, Na+,K(+)-ATPase activity decreased linearly as a function of the decrease in PCr/Pi (r = 0.95). Levels of lipid peroxidation products (conjugated dienes and fluorescent compounds) increased significantly as PCr/Pi decreased. These data suggest that below a critical threshold value of oxidative metabolism there are progressive changes in brain cell membrane structure and function during cerebral hypoxia, and demonstrate that membrane alterations occur prior to changes in cellular ATP levels.

Animals↗