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Biomedical subjects

A D Edwards

Publications and source records attributed to A D Edwards.

At least 109 records · Page 6Linked to original sources

Mild hypothermia after severe transient hypoxia-ischemia ameliorates delayed cerebral energy failure in the newborn piglet.

Severely birth-asphyxiated human infants develop delayed ("secondary") cerebral energy failure, which carries a poor prognosis, during the first few days of life. This study tested the hypothesis that mild hypothermia after severe transient cerebral hypoxia-ischemia decreases the severity of delayed energy failure in the newborn piglet. Six piglets underwent temporary occlusion of the common carotid arteries and hypoxemia. Resuscitation was started when cerebral [phosphocreatine (PCr)]/[inorganic phosphate (Pi)] as determined by phosphorus magnetic resonance spectroscopy had fallen almost to zero and [nucleotide triphosphate (NTP)]/[exchangeable phosphate pool (EPP)] had fallen below about 30% of baseline. Rectal and tympanic temperatures were then reduced to 35 degrees C for 12 h after which normothermia (38.5 degrees C) was resumed. Spectroscopy results over the next 64 h were compared with previously established data from 12 piglets similarly subjected to transient cerebral hypoxia-ischemia, but maintained normothermic, and six sham-operated controls. The mean severity of the primary insult (judged by the time integral of depletion of [NTP]/[EPP]) was similar in the hypothermic and normothermic groups. In the normothermic group, [PCr]/[Pi] and [NTP]/[EPP] recovered after the acute insult and then fell again. Minimum values for these variables observed between 24 and 48 h were significantly higher in the hypothermic group and not significantly different from the control values (p < 0.05, analysis of variance). A large reduction in secondary energy failure relative to the extent of the primary insult was shown and no further fall in either [PCr]/[Pi] or [NTP]/[EPP] took place up to 64 h in the hypothermic piglets.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Cerebral blood volume response to changes in carbon dioxide tension before and during cardiopulmonary bypass in children, investigated by near infrared spectroscopy.

Neurological impairment may occur following cardiopulmonary bypass (CPB) and the effect of CPB on cerebrovascular control may be important in the mechanism of cerebral injury. We have used near infrared spectroscopy (NIRS) to observe cerebral haemodynamics non-invasively before and during CPB. We measured the change in cerebral blood volume (CBV) associated with changing PaCO2 (CBVR). Patients (n = 19) were aged from 1 to 135 (median 14) months. The cerebral blood volume response was determined pre-operatively at normothermia under the influence of standardised anaesthesia employing isoflurane (up to ET conc 0.5%) and during steady-state hypothermic bypass (22-32 degrees C) at an arterial pump flow rate of 1.9-2.4 lm-2.min-1. Complete data was available for 10 patients. The relation between CBV, arterial carbon dioxide tension (PaCO2), mean arterial pressure (MAP) and central venous pressure (CVP) was examined using analysis of covariance (P < or = 0.05) was accepted as significant). The change in CBV associated with changing PaCO2 was corrected for the effects of MAP and CVP. Preoperatively the median CBVR was 0.130 (25th-75th percentile 0.079-0.243) ml.100 g-1.kPa-1 and during hypothermic bypass the median CBVR was 0.093 (25th-75th percentile 0.026-0.255) ml.100 g-1.kPa-1. These values were compared with our reference range derived for normal conscious children using the Kruskal-Wallis test. There was not statistically significant difference between the three groups (P = 0.35). These results, indicating preservation of CBVR during the conditions of anaesthesia and bypass used, are consistent with the observations of previous authors who measured cerebral blood flow response to carbon dioxide by a variety of other methods. Near infrared spectroscopy is proving to be a reliable, non-invasive technique for the investigation of cerebral haemodynamics during CPB.

Adolescent↗

Early detection of cerebral infarction and hypoxic ischemic encephalopathy in neonates using diffusion-weighted magnetic resonance imaging.

Twelve newborn infants with clinical evidence of hypoxic ischemic brain injury had conventional and diffusion-weighted magnetic resonance imaging (MRI) performed one to six (median two) days and 7-42 days after birth. The extent and conspicuity of the early abnormalities was greater with diffusion-weighted than with conventional imaging in each of the four infants with neonatal infarction and in four of the infants with Grades II or III hypoxic ischemic encephalopathy (HIE). No abnormality was seen with either technique in the other four infants who had Grades I or II HIE. Diffusion weighted MRI may be important for the early diagnosis and grading of infants with hypoxic ischemic brain injury.

Asphyxia Neonatorum↗

Relation between frequency of uterine contractions and human fetal cerebral oxygen saturation studied during labour by near infrared spectroscopy.

OBJECTIVE: To investigate the effect of the frequency of uterine contractions on fetal cerebral oxygenation, using near infrared spectroscopy. DESIGN: An observational study relating changes in the fetal cerebral concentrations of oxyhaemoglobin and deoxyhaemoglobin, measured from the start of one contraction to that of the next, to the time interval between contraction peaks observed by external tocography. SETTING: A teaching hospital obstetric and neonatal unit. SUBJECTS: Ten term fetuses during labour. RESULTS: Changes in cerebral oxyhaemoglobin concentration were positively, and in deoxyhaemoglobin negatively, correlated with the time interval between contractions (P < 0.001). A mean contraction interval of 2.3 min was found below which the concentration of oxyhaemoglobin usually fell and that of deoxyhaemoglobin rose, indicating a fall in cerebral haemoglobin saturation. Conversely, longer contraction intervals were associated with findings indicative of a rise in cerebral haemoglobin saturation. CONCLUSION: Short contraction intervals (< 2.3 min) were associated with a decrease, and longer contraction intervals with an increase in fetal cerebral oxygen saturation. Contractions occurring repeatedly at intervals less than 2.3 min are likely to result in progressive cerebral desaturation.

Brain Chemistry↗

Quantification of adult cerebral hemodynamics by near-infrared spectroscopy.

Near-infrared spectroscopy was used to measure global cerebral blood flow and volume in 10 healthy adult volunteers. High- and low-cerebral blood flow compartments were detected with mean flows for all 10 subjects of 59 +/- 21 (SD) and 11 +/- 4 ml.100 g-1.min-1, respectively. The mean cerebral blood volume of the group was 2.85 +/- 0.97 ml/100 g. Analysis of spontaneous changes in the cerebral concentrations of oxyhemoglobin and deoxyhemoglobin demonstrated strong correlations between respiratory rate and the oscillation frequency of cerebral oxyhemoglobin concentration (r = 0.99) and arterial oxygen saturation (SaO2) (r = 0.99). An estimate of the mean cerebral oxygen saturation for all subjects averaged 59.4 +/- 12.4% when their mean SaO2 was 91.8 +/- 2.4% (equivalent to 67.6 +/- 13.8% at a normoxic SaO2 of 98%). These results demonstrate that near-infrared spectroscopy can be used as a noninvasive bedside technique for both qualitative and quantitative evaluation of cerebral hemodynamics and oxygenation in adults.

Adult↗

Delayed ("secondary") cerebral energy failure after acute hypoxia-ischemia in the newborn piglet: continuous 48-hour studies by phosphorus magnetic resonance spectroscopy.

Phosphorous (31P) spectra from the brains of severely birth-asphyxiated human infants are commonly normal on the first day of life. Later, cerebral energy failure develops, which carries a serious prognosis. The main purpose of this study was to test the hypothesis that this delayed ("secondary") energy failure could be reproduced in the newborn piglet after a severe acute reversed cerebral hypoxic-ischemic insult. Twelve piglets were subjected to temporary occlusion of the common carotid arteries and hypoxemia [mean arterial PO2 3.1 (SD 0.6) kPa]. Mean cerebral phosphocreatine concentration [PCr]/inorganic orthophosphate concentration [Pi] decreased from 1.40 (SD 0.29) to 0.01 (SD 0.02), and nucleotide triphosphate concentration [NTP]/exchangeable phosphate pool concentration [EPP] decreased from 0.19 (SD 0.02) to 0.06 (SD 0.04) (p < 0.001 for each decrease). On reperfusion and reoxygenation of the brain, mean [PCr]/[Pi] and [NTP]/[EPP] returned to baseline. Observations continuing for the next 48 h showed that [PCr]/[Pi] again decreased, in spite of normal arterial PO2, mean arterial blood pressure, and blood glucose, to 0.62 (SD 0.61) at 24 h (p < 0.01) and 0.49 (SD 0.37) at 48 h (p < 0.001). [NTP]/[EPP] also decreased, but to a lesser degree. Intracellular pH remained unchanged. These findings appeared identical with those seen in birth-asphyxiated human infants. No changes in cerebral metabolite concentrations took place in six control piglets. The severity of secondary energy failure, as judged by the lowest [PCr]/[Pi] recorded at 24-48 h, was directly related to the extent of acute energy depletion, obtained as the time integral of reduction in [NTP]/[EPP] (p < 0.0001). This animal model of secondary energy failure may prove useful for testing cerebroprotective strategies.

Acute Disease↗

The clinical role of near infrared spectroscopy.

Near infrared spectroscopy is a non-invasive bedside technique which allows cotside observation of cerebral haemodynamics and oxygenation in sick newborn infants. Methods have been described for measurement of cerebral blood flow and volume, as well as other tests of the cerebral circulation. The techniques is still under intensive development and further advances and refinements can be expected, but a present it is essentially a technique for research and investigations rather than a clinical tool.

Cerebrovascular Circulation↗

Measurement of adult cerebral haemodynamics using near infrared spectroscopy.

Near infrared spectroscopy (NIRS) is a non invasive, portable, safe technique for monitoring cerebral oxygenation and haemodynamics. Since it does not involve the use of ionising radiation it may be used repeatedly to produce serial measurements of CBF and CBV in patients, and continuously to provide trend data about cerebral circulation changes. NIRS allows measurements to be made at the bedside with minimal disturbance to other monitoring and treatment procedures. Although regional information is not yet available, good time resolution allows rapid changes in cerebral haemodynamics to be observed.

Adult↗

Cerebral hemodynamics during cardiopulmonary bypass in children using near-infrared spectroscopy.

We describe a new noninvasive method using near-infrared spectroscopy for monitoring cerebral hemodynamics during cardiopulmonary bypass in children. All patients were undergoing open heart operations for repair of congenital heart defects. Standardized anesthesia, an alpha-stat method of blood gas management, and nonpulsatile flow were used in all cases. All measurements during bypass were made after steady-state conditions had been reached. Cerebral blood flow was measured on 13 occasions in 4 children, aged between 4 and 10 months (median, 5 months). Values of 15.9 to 53.5 mL x 100 g-1 x min-1 were obtained. Cerebral blood volume was measured in 1 patient, aged 4 months. Volumes of 4.3 to 8.0 mL x 100 g-1 were obtained on bypass at full pump flow (2.4 L.min-1 x m-2). On bypass at half flow, the volume increased to 14.7 mL x 100 g-1. Change in cerebral blood volume with changing carbon dioxide tension (CBVR) was measured in 13 patients aged from 1 to 90 months (median, 13.5 months). Preoperatively, CBVR was 0.12 +/- 0.07 mL x 100 g-1 x kPa-1 and was independent of mean arterial pressure, which remained between 40 and 80 mm Hg in all cases. During hypothermic bypass (25 degrees C), CBVR was significantly reduced to 0.05 +/- 0.02 mL x 100 g-1 x kPa-1. In addition, there were three values at mean arterial pressure of lower than 40 mm Hg in which CBVR was negative (-0.04 +/- 0.01 mL x 100 g-1 x kPa-1). We conclude that near-infrared spectroscopy is useful for the noninvasive investigation of cerebral hemodynamics during cardiopulmonary bypass.

Carbon Dioxide↗

Relation between ultrasound appearance of the brain of very preterm infants and neurodevelopmental impairment at eight years.

The relation between the ultrasound appearance of the brain and neurodevelopmental outcome at eight years of age was investigated in 206 infants born between 1979 and 1982 at < 33 weeks gestation (600 to 2500g birthweights). Only 4 per cent of the 112 infants with normal scans at discharge from the neonatal unit developed major, disabling impairment. No significant adverse effect of uncomplicated periventricular haemorrhage was detected. The probability of a major impairment in infants with ventricular dilatation or hydrocephalus was 27 per cent, and 69 per cent in those with cerebral atrophy. 44 per cent of the children demonstrated significant differences in their cognitive processing skills, which appeared capable of affecting learning and may possibly have been caused by undetected hypoxic-ischaemic damage to callosal fibres.

Achievement↗

Measurement of hemoglobin flow and blood flow by near-infrared spectroscopy.

A noninvasive method of measuring hemoglobin flow through an organ by near-infrared spectroscopy (NIRS) is described that allows blood flow to be calculated. The method is derived from the Fick principle and uses a small change in arterial oxyhemoglobin concentration (brought about by a change in the fractional inspired O2 concentration) as an intravascular tracer. Changes in deoxyhemoglobin and oxyhemoglobin concentrations are quantified by monitoring variations in the absorption of near-infrared light in the organ, thus providing a measure of tracer accumulation. The tracer input function is calculated from the change in arterial O2 saturation, measured by pulse oximetry. The method was used to determine hemoglobin flow in the forearms of six healthy young adults on 10 occasions. Forearm hemoglobin flow ranged from 22.5 to 82.6 mumol.l-1.min-1. Calculated forearm blood flow ranged from 1.01 to 4.01 ml.100 g-1.min-1. For comparison, forearm blood flow was measured by venous occlusion plethysmography, and the relation between flow calculated by NIRS (y) and plethysmography (x) was y = 0.93x + 0.30 (r2 = 0.95). The mean difference between the methods was 0.14 ml.100 g-1.min-1. The technique may be widely applicable.

Adult↗

Comparison between near infrared spectroscopy and 133Xenon clearance for estimation of cerebral blood flow in critically ill preterm infants.

Estimations of cerebral blood flow were performed by both near infrared spectroscopy and 133xenon clearance on 12 occasions in nine critically ill premature infants (26-29 gestational wk) who required mechanical ventilation and supplemental oxygen. For each study, one determination of cerebral blood flow by 133xenon was compared with the mean of two to five measurements by near infrared done within 1-19 (median 5) h. 133Xenon measurements ranged from 9.6-16.9 mL/100 g/min, and mean near infrared measurements ranged from 8.6-25.0 mL/100 g/min. There was a significant correlation between the two sets of measurements (r = 0.80, p < 0.001). The mean difference between the methods was 1.6 mL/100 g/min, and the 95% limits of agreement were -0.5-3.8 mL/100 g/min. This study showed that cerebral blood flow can be measured noninvasively in critically ill premature infants at the cotside by near infrared spectroscopy and by the 133xenon clearance technique. The methods give comparable results.

Brain Ischemia↗

Effect of indomethacin on cerebral oxidized cytochrome oxidase in preterm infants.

To determine the effect of i.v. indomethacin on cerebral intracellular oxygenation, as judged by changes in the concentration of oxidized cytochrome oxidase, studies were performed using near-infrared spectroscopy on 15 infants of 23 to 29 wk gestation, aged 8 to 30 d, who required the drug for closure of a patent ductus arteriosus. Indomethacin caused significant (p < 0.01) falls in cerebral blood flow, oxygen delivery, and blood volume and its reactivity to changes in arterial carbon dioxide tension, as previously reported. In 11 of the 15 infants, significant (p < 0.01) falls of 0.18 to 0.92 mumol.L-1 in the concentration of oxidized cytochrome oxidase were observed. Parallel experiments on synaptosomes derived from rat brain showed that indomethacin was most unlikely to have had a direct effect on mitochondrial respiration. These results are consistent with the hypothesis that the observed falls in the concentration of oxidized cytochrome oxidase resulted from hemodynamic perturbations that reduced cerebral intracellular oxygenation.

Animals↗