Biomedical subjects

O D Saugstad

Publications and source records attributed to O D Saugstad.

At least 73 records · Page 4Linked to original sources

PubMed1998

Hypoxanthine levels in vitreous humor: a study of influencing factors in sudden infant death syndrome.

Elevated hypoxanthine (Hx) levels in the vitreous humor of victims of the sudden infant death syndrome (SIDS) have been been claimed to indicate hypoxia before death. An important methodologic problem is the temperature-dependent Hx increase after death. Although most previous studies have corrected for expected postmortem Hx increase, the aim of the present study was to omit this problem by matching the subjects of the different groups studied for similar postmortem time. Thirteen cases of violent death, 11 cases of borderline SIDS, 22 cases of death from infectious disease, and 17 cases of death from heart/lung disease were compared with a 3-fold number of SIDS cases. To investigate the impact of environmental factors on the Hx levels of the SIDS cases, the following possible confounding factors were investigated: attempt to resuscitate, slight infections before death, sleeping position, and time of the day when found dead. To investigate whether the size of the eyeball would influence the Hx level, five cases of violent death in children were compared with 15 adults who died suddenly. The vitreous humor Hx level was significantly higher in SIDS victims than in cases of violent death (p < 0.01) and deaths due to heart/lung disease (p < 0.01), whereas no such difference was found either between SIDS and borderline SIDS or SIDS and infectious death. There were no differences between any of the subgroups of SIDS victims. The vitreous humor Hx level in small children and adults did not differ. The findings raise the question of possible similarities in death mechanism in SIDS and infectious death.

Age Factors↗

PubMed1998

Pulmonary hemodynamics and plasma endothelin-1 during hypoxemia and reoxygenation with room air or 100% oxygen in a piglet model.

The immediate effect on the pulmonary circulation of reoxygenation with either room air or 100% O2 was studied in newborn piglets. Hypoxemia was induced by ventilation with 8% O2 until base excess was <-20 mmol/L or mean arterial blood pressure was <20 mm Hg. Reoxygenation was performed with either room air (n = 9) or 100% O2 (n = 9). Mean pulmonary artery pressure increased during hypoxemia (p = 0.012). After 5 min of reoxygenation, pulmonary artery pressure increased further from 24 +/- 2 mm Hg at the end of hypoxemia to 35 +/- 3 mm Hg (p = 0.0077 versus baseline) in the room air group and from 27 +/- 3 mm Hg at the end of hypoxemia to 30 +/- 2 mm Hg (p = 0.011 versus baseline) in the O2 group (NS between groups). Pulmonary vascular resistance index increased (p = 0.0005) during hypoxemia. During early reoxygenation pulmonary vascular resistance index decreased rapidly to values comparable to baseline within 5 min of reoxygenation in both groups (NS between groups). Plasma endothelin-1 (ET-1) decreased during hypoxemia from 1.5 +/- 0.1 ng/L at baseline to 1.2 +/- 0.1 ng/L at the end of hypoxemia (p = 0.003). After 30 min of reoxygenation plasma ET-1 increased to 1.8 +/- 0.3 and 1.5 +/- 0.2 ng/L in the room air and O2 groups, respectively (p = 0.0077 in each group versus end hypoxemia; NS between groups). We conclude that hypoxemic pulmonary hypertension and plasma ET-1 normalizes as quickly when reoxygenation is performed with room air as with 100% O2 in this hypoxia model with newborn piglets.

Acid-Base Equilibrium↗

PubMed1998

Leptin levels in pregnant women and newborn infants: gender differences and reduction during the neonatal period.

OBJECTIVE: Leptin is a highly hydrophilic protein that circulates in plasma as a 16-kDa protein. It is produced in adipose tissue and also recently described to be synthesized by placental tissue. Plasma concentration of leptin is positively correlated to body fat mass, and administration of recombinant leptin to mice indicates that leptin participates in the regulation of food intake and energy expenditure. Leptin may have a role during initiation of human pubertal development. Gender differences have been reported among adults as well as among children, even after correction for body fat content. Little is known about variation in leptin levels during pregnancy or the level or function of leptin in the growing fetus and infants. The aim of the present study was to examine plasma concentration of leptin in pregnant women and their newborn infants during the first 3 months of life, and to relate plasma leptin concentration to body weight and gender during this period. MATERIALS AND METHODS: Among 609 women recruited to study the effect of very long-chain n-3 fatty acids during pregnancy, 180 women were selected to study leptin as well. The women were all healthy and nulli- or primiparas, and 16% were smokers. The study was randomized and double-blinded, and the participants received either 10 mL of cod liver oil (Peter Moller, avd.av Orkla ASA, Oslo, Norway) daily or the same amount of corn oil. Blood samples were taken from the mothers during pregnancy in weeks 18 and 35, and from the umbilical cord and from 4- and 14-week-old infants. The mothers' body mass index (BMI) at 18 and 35 weeks of pregnancy was calculated by using body weight recorded within 1 week or, if this was missing, by using means from weights at the closest time points before and after the sampling. The infants were weighed and measured at local health care centers. Plasma leptin concentration was measured by radio immunoassay (Linco Research, St Charles, MO) using recombinant 125I-leptin as tracer. RESULTS: We found no differences between the group receiving cod liver oil and the group receiving corn oil in any of the measured variables; thus, the groups are treated statistically as one. Leptin concentration in maternal plasma increased during pregnancy from 15.5 +/- 9.0 microg/L (n = 175) in week 18 to 17.7 +/- 10.7 microg/L (n = 166) in week 35. Mothers, pregnant with female fetuses (n = 77), had a significant increase in plasma leptin concentration, from 15.5 +/- 8.8 microg/L (n = 83) at 18 weeks to 18.5 +/- 10.9 microg/L (n = 80) at 35 weeks of pregnancy, whereas in mothers pregnant with male fetuses, the increase was insignificant (15.4 +/- 9.3 microg/L (n = 92) to 17.0 +/- 10.5 microg/L (n = 86). BMI increased during the same time period, from 24.2 +/- 3.3 kg/m to 27.8 +/- 3.8 kg/m (n = 174). There was a significant correlation between BMI and plasma leptin concentration at 18 weeks (r = 0.54, n = 169) and at 35 weeks (r = 0.45, n = 160), but we found no change in the relative leptin concentration (plasma leptin concentration/BMI) from week 18 to week 35. We found no significant difference between smokers and nonsmokers in plasma leptin concentration, neither at 18 nor 35 weeks of pregnancy. Gender differences in plasma leptin concentration was present already at birth in umbilical cord plasma (10.8 +/- 9.2 microg/L for girls [n = 65] vs 7.6 +/- 6.6 microg/L for boys [n = 74]). We also observed gender differences in plasma leptin concentration at 4 weeks (3.9 +/- 1.8 microg/L, n = 68 vs 3.2 +/- 1.8 microg/L, n = 71) and 14 weeks of age (4.9 +/- 2.1 microg/L, n = 61 vs 4.1 +/- 3.1 microg/L, n = 73). Plasma leptin levels at 4 and 14 weeks were lower than the level in umbilical cord plasma (n = 101). An increase in plasma leptin concentration was observed from 4 to 14 weeks of age, both for girls (n = 48) and for boys (n = 60). Leptin concentration in umbilical cord plasma correlated with birth weight (r = 0.44, n = 139), and there was significant corre

Adipose Tissue↗

PubMed1998

Resuscitation of asphyxiated newborn infants with room air or oxygen: an international controlled trial: the Resair 2 study.

OBJECTIVE: Birth asphyxia represents a serious problem worldwide, resulting in approximately 1 million deaths and an equal number of serious sequelae annually. It is therefore important to develop new and better ways to treat asphyxia. Resuscitation after birth asphyxia traditionally has been carried out with 100% oxygen, and most guidelines and textbooks recommend this; however, the scientific background for this has never been established. On the contrary, theoretic considerations indicate that resuscitation with high oxygen concentrations could have detrimental effects. We have performed a series of animal studies as well as one pilot study indicating that resuscitation can be performed with room air just as efficiently as with 100% oxygen. To test this more thoroughly, we organized a multicenter study and hypothesized that room air is superior to 100% oxygen when asphyxiated newborn infants are resuscitated. METHODOLOGY: In a prospective, international, controlled multicenter study including 11 centers from six countries, asphyxiated newborn infants with birth weight >999 g were allocated to resuscitation with either room air or 100% oxygen. The study was not blinded, and the patients were allocated to one of the two treatment groups according to date of birth. Those born on even dates were resuscitated with room air and those born on odd dates with 100% oxygen. Informed consent was not obtained until after the initial resuscitation, an arrangement in agreement with the new proposal of the US Food and Drug Administration's rules governing investigational drugs and medical devices to permit clinical research on emergency care without the consent of subjects. The protocol was approved by the ethical committees at each participating center. Entry criterion was apnea or gasping with heart rate <80 beats per minute at birth necessitating resuscitation. Exclusion criteria were birth weight <1000 g, lethal anomalies, hydrops, cyanotic congenital heart defects, and stillbirths. Primary outcome measures were death within 1 week and/or presence of hypoxic-ischemic encephalopathy, grade II or III, according to a modification of Sarnat and Sarnat. Secondary outcome measures were Apgar score at 5 minutes, heart rate at 90 seconds, time to first breath, time to first cry, duration of resuscitation, arterial blood gases and acid base status at 10 and 30 minutes of age, and abnormal neurologic examination at 4 weeks. The existing routines for resuscitation in each participating unit were followed, and the ventilation techniques described by the American Heart Association were used as guidelines aiming at a frequency of manual ventilation of 40 to 60 breaths per minute. RESULTS: Forms for 703 enrolled infants from 11 centers were received by the steering committee. All 94 patients from one of the centers were excluded because of violation of the inclusion criteria in 86 of these. Therefore, the final number of infants enrolled in the study was 609 (from 10 centers), with 288 in the room air group and 321 in the oxygen group. Median (5 to 95 percentile) gestational ages were 38 (32.0 to 42.0) and 38 (31.1 to 41.5) weeks (NS), and birth weights were 2600 (1320 to 4078) g and 2560 (1303 to 3900) g (NS) in the room air and oxygen groups, respectively. There were 46% girls in the room air and 41% in the oxygen group (NS). Mortality in the first 7 days of life was 12.2% and 15.0% in the room air and oxygen groups, respectively; adjusted odds ratio (OR) = 0.82 with 95% confidence intervals (CI) = 0.50-1.35. Neonatal mortality was 13.9% and 19.0%; adjusted OR = 0. 72 with 95% CI = 0.45-1.15. Death within 7 days of life and/or moderate or severe hypoxic-ischemic encephalopathy (primary outcome measure) was seen in 21.2% in the room air group and in 23.7% in the oxygen group; OR = 0.94 with 95% CI = 0.63-1.40. (ABSTRACT TRUNCATED)

Acid-Base Equilibrium↗

PubMed1998

Resuscitation with room-air or oxygen supplementation.

An accumulating body of data indicates that optimal newborn resuscitation is not performed with 100% oxygen. On the contrary, ambient air seems to have several advantages compared with supplemental oxygen. Present guidelines on newborn resuscitation should be critically reviewed and revised according to scientific evidence.

Air↗

PubMed1997

Ascorbic acid enhances hydroxyl radical formation in iron-fortified infant cereals and infant formulas.

UNLABELLED: Infant cereals and formulas are usually fortified with iron to prevent iron deficiency. To enhance iron bioavailability, supplemental ascorbic acid is recommended. Ascorbic acid is considered to be an antioxidant in vivo, but has pro-oxidant effects when exposed to non-protein-bound iron. We measured formation of free radicals in cereals and infant formulas after addition of ascorbic acid. The production of hydroxyl radicals was assessed by hydroxylation of salicylic acid to 2.5-dihydroxybenzoic acid (2,5-DHBA). Production of 2.5-DHBA increased with increasing ascorbic acid doses added. Addition of 0.8 mM ascorbic acid to breast milk produced less radicals (0.03 +/- 0.05 microM) than addition of ascorbic acid to low-iron formula (0.13 +/- 0.08 microM. P = 0.019), medium-iron formula (0.34 +/- 0.12 microM, P < 0.0001) or high-iron formula (0.44 +/- 0.08 microM. P < 0.0001). Even when iron content in breast milk was adjusted to a level comparable with that of formulas, production of 2,5-DHBA was lower. Breast milk seems to contain substances that reduce hydroxyl radical formation. CONCLUSION: Supplemental ascorbic acid causes hydroxyl radical formation in iron-fortified infant nutrients in vitro.

Ascorbic Acid↗

PubMed1997

Effects of hypoxemia and reoxygenation with 21% or 100% oxygen in newborn piglets: extracellular hypoxanthine in cerebral cortex and femoral muscle.

OBJECTIVE: To determine whether reoxygenation with an FIO2 of 0.21 (21% oxygen) is preferable to an FIO2 of 1.0 (100% oxygen) in normalizing brain and muscle hypoxia in the newborn. DESIGN: Prospective, randomized, animal study. SETTING: Hospital surgical research laboratory. SUBJECTS: Twenty-six anesthetized, mechanically ventilated, domestic piglets, 2 to 5 days of age. INTERVENTIONS: The piglets were randomized to control or hypoxemia groups. Hypoxemia was induced by ventilating the piglets with 8% oxygen in nitrogen, which was continued until mean arterial pressure decreased to <20 mm Hg. After hypoxemia, the piglets were further randomized to receive reoxygenation with an FIO2 of 0.21 (21% oxygen group, n = 9) or an FIO2 of 1.0 for 30 mins followed by an FIO2 of 0.21 (100% oxygen group, n = 9), and followed for 5 hrs. The piglets in the control group were mechanically ventilated with 21% oxygen (n = 8). MEASUREMENTS AND MAIN RESULTS: We measured extracellular concentrations of hypoxanthine in the cerebral cortex and femoral muscle (in vivo microdialysis), plasma hypoxanthine concentrations, cerebral arterial-venous differences for hypoxanthine, acid base balances, arterial and venous (sagittal sinus) blood gases, and mean arterial pressures. The lowest pH values of 6.91 +/- 0.11 (21% oxygen group, mean +/- SD) and 6.90 +/- 0.07 (100% oxygen group) were reached at the end of hypoxemia and then normalized during the reoxygenation period. Plasma hypoxanthine increased during hypoxemia from 28.1 +/- 9.3 to 119.1 +/- 31.9 micromol/L in the 21% oxygen group (p < .001) and from 32.6 +/0- 14.5 to 135.0 +/- 31.4 micromol/L in the 100% oxygen group (p <.001). Plasma hypoxanthine concentrations then normalized over the next 2 hrs in both groups. In the cerebral cortex, extracellular concentrations of hypoxanthine increased during hypoxemia from 3.9 +/- 2.8 to 20.2 +/- 7.4 micromol/L in the 21% oxygen group (p < .001) and from 5.9 +/- 5.0 to 25.1 +/- 7.1 micromol/L in the 100% oxygen group (p < .001). In contrast to plasma hypoxanthine, extracellular hypoxanthine in the cerebral cortex increased significantly further during early reoxygenation, and, within the first 30 mins, reached maximum values of 24.9 +/- 6.3 micromol/L in the 21% oxygen group (p < .01) and 34.8 +/- 10.9 micromol/L in the 100% oxygen group (p < .001). This increase was significantly larger in the 100% oxygen group than in the 21% oxygen group (9.7 +/- 4.7 vs. 4.7 +/- 2.6 micromol/L, p < .05). There were no significant differences between the two reoxygenated groups in duration of hypoxemia, hypoxanthine concentrations in femoral muscle, plasma hypoxanthine concentrations, pH, or mean arterial pressure. The cerebral arterial-venous difference for hypoxanthine was positive both at baseline, at the end of hypoxemia, and after 30 mins and 300 mins of reoxygenation, and no differences were found between the two reoxygenated groups. CONCLUSIONS: Significantly higher extracellular concentrations of hypoxanthine were found in the cerebral cortex during the initial period of reoxygenation with 100% oxygen compared with 21% oxygen. Hypoxanthine is a marker of hypoxia, and reflects the intracellular energy status. These results therefore suggest a possibly more severe impairment of energy metabolism in the cerebral cortex or an increased blood-brain barrier damage during reoxygenation with 100% oxygen compared with 21% oxygen in this newborn piglet hypoxia model.

Animals↗

PubMed1997

Bronchopulmonary dysplasia and oxidative stress: are we closer to an understanding of the pathogenesis of BPD?

In recent years a body of data has accumulated, linking the development of bronchopulmonary dysplasia (BPD) to increased oxidative stress in the first few days after birth, since high concentrations of metabolites reflecting increased peroxidation products such as pentane, ethane, protein carbonyl, o-tyrosine, allantoin and F2-isoprostanes, as well as low levels of glutathione and sulfhydryl/total protein ratio, also reflecting increased oxidative load, have been found in the premature infants at risk of or developing BPD. Oxidative stress seems to increase lung antioxidants in some experimental models of BPD and hyperoxia affects foetal lung growth. There are similarities between inflammation and hypoxia/reoxygenation, since both activate a number of inflammatory mediators such as cytokines and adhesion molecules, some of which are found in high concentrations in tracheal aspirate fluid of infants developing BPD. Surfactant production and function are also altered by both hyperoxia and reactive oxygen species per se, making the lungs more vulnerable to injury. This new knowledge may result in new and more efficient therapeutic approaches, hopefully leading to the eradication of BPD in the near future.

Animals↗

PubMed1997

Near-infrared monitoring of cerebral tissue oxygen saturation and blood volume in newborn piglets.

Near-infrared spectrophotometry (NIRS) potentially provides a tool for noninvasive tissue oxygenation and blood volume monitoring. Cerebral monitoring could be useful in the prevention of hypoxic ischemic brain injury in newborns. This study sought to validate such NIRS measurements in normoventilated, hypocapnic, and hypoxemic states in the brain of newborn piglets vs. arterial (SaO2) and sagittal sinus blood hemoglobin saturation (SssO2) and blood volume measurements with 99mTc-labeled erythrocytes. NIRS measurements of cerebral blood volume (CBV) were performed with both oxyhemoglobin and indocyanine green as tracers, and changes in CBV were monitored by following the change in the concentration of total hemoglobin (i.e., oxyhemoglobin + deoxyhemoglobin). NIRS CBV measurements did not correlate well with the radioactive measurements. NIRS measurements of oxygenation, however, correlated well with a weighted mean value of SaO2 and SssO2 (r = 0.90; P < 0.0001). Multiple linear regression of the oxygenation index (i.e., oxyhemoglobin - deoxyhemoglobin) on SaO2 and SssO2 suggested that NIRS sees hemoglobin in tissue in a venous-to-arterial ratio of 2:1. Therefore, in this study, NIRS reliably monitored changes in cerebral tissue oxygenation but not in CBV.

Animals↗

PubMed1997

Acute effects on systemic and pulmonary hemodynamics of intratracheal instillation of porcine surfactant or saline in surfactant-depleted newborn piglets.

Surfactant instillation may affect systemic and pulmonary hemodynamics. The aim of this study was to investigate whether this effect is specific to surfactant or if it can be triggered by instillation of the same volume of saline. Piglets 3-5-d-old were subjected to repeated lung lavage using 20 mL/kg 0.9% saline until the partial pressure of arterial O2 was < 10 kPa and partial pressure of arterial CO2 was between 4.0 and 6.0 kPa with fraction of inspired oxygen (FiO2) 1.0 and peak inspiratory pressure 25 cm H2O. Porcine surfactant 200 mg/kg (80 mg/mL) or the same volume of 0.9% saline was instilled into the lungs through a feeding catheter entered through the endotracheal tube. Mean arterial blood pressure, pulmonary artery pressure, and cardiac output were measured continuously. There was a significant decrease in mean arterial blood pressure from 67 (+/- 13) mm Hg to 52 (+/- 18) mm Hg (p < 0.05) 210 s after instillation of surfactant. Systemic vascular resistance decreased from 0.42 (+/- 0.18) to 0.34 (+/- 0.18) mm Hg x mL-1 x min x kg (p < 0.05) from 0 min to 180 s after instillation of surfactant. In the group receiving saline instillations there were no significant changes in mean arterial blood pressure or systemic vascular resistance. A transient but significant increase in mean pulmonary artery pressure was seen 120 s after instillation in both groups with a return to presurfactant level 240 s after instillation. Pulmonary vascular resistance increased transiently and significantly only in the group receiving surfactant. We conclude that porcine surfactant causes a decrease in systemic vascular resistance, resulting in a decrease in mean arterial blood pressure in newborn lung-lavaged piglets not seen after instillation of the same volume of saline.

Animals↗

PubMed1997

Nitric oxide contributes to surfactant-induced vasodilation in surfactant-depleted newborn piglets.

To investigate whether nitric oxide (NO) is involved in surfactant-induced systemic and pulmonary vasodilatation in newborn piglets with surfactant deficiency, 2-6-d-old piglets were subjected to repeated saline lung lavages. They were then randomly assigned to one of two groups (seven in each group): the N(omega)-nitro-L-arginine methyl ester (L-NAME) group received 3 mg/kg L-NAME i.v. 45 min before endotracheal instillation of 200 mg/kg porcine surfactant; the saline group received saline i.v. at the same time point, and instillation of 200 mg/kg surfactant. Mean arterial blood pressure, systemic vascular resistance, pulmonary arterial pressure, and pulmonary vascular resistance increased significantly after injection of L-NAME (all p < 0.01), whereas the cardiac index decreased significantly (p < 0.05). Saline injection did not change any variable. Significant decreases in mean arterial blood pressure (from a mean +/- SD of 66 +/- 10 to 53 +/- 9 mm Hg, p < 0.01), pulmonary arterial pressure (from 29 +/- 6 to 23 +/- 6 mm Hg, p < 0.01), and systemic vascular resistance (from 0.40 +/- 0.13 to 0.33 +/- 0.12 mm Hg/mL/min/kg, p < 0.05) were observed only in the saline group after surfactant instillation, whereas the decrease in pulmonary vascular resistance was not significant after surfactant instillation (p = 0.06). In contrast to the saline group, these variables were not modified in the L-NAME group after surfactant instillation. We conclude that the vasodilatory effect of porcine surfactant instillation in newborn piglets with surfactant deficiency is associated with activation of NO synthase.

Animals↗

PubMed1997

Plasma hypoxanthine reacts more abruptly to changes in oxygenation than base deficit and uric acid in newborn piglets.

Previously, high postmortem concentrations of hypoxanthine have been found in vitreous humor of children dying from sudden infant death syndrome (SIDS). We wanted to investigate further the accumulation of hypoxanthine in vitreous humor during hypoxia. Twenty-four piglets aged 9-15 days were exposed to continuous hypoxemia (180 min 11% O2, n = 6), long interval intermittent hypoxemia (60 min 11% O2, 20 min room air, n = 7) or short interval intermittent hypoxemia (10 min 9% O2, 10 min room air with (n = 6) or without (n = 5) superimposed ligation of both carotid arteries). The increase in vitreous humor Hyp was four-fold higher (p < 0.01) with ligation of the carotid arteries (14 +/- 2.4 to 38 +/- 8.9 mumol/l) than without ligation (15 +/- 2.8 to 21 +/- 5.9 mumol/l). During continuous hypoxemia, plasma Hyp (r = 0.85), Xa (r = 0.89) uric acid (UA) (r = 0.85), and base deficit (BD) (r = 0.78) increased almost linearly (p < 0.001). Plasma Hyp responded more abruptly to changes in oxygenation than base deficit (BD) and UA. Ligation of the carotid arteries had a strong impact on Hyp accumulation in vitreous humor, suggesting that vitreous humor Hyp is not merely a filtration product of plasma Hyp, but reflects local hypoxia/ischemia in the eye.

Acids↗

PubMed1997

The importance of the measurement of ATP depletion and subsequent cell damage with an estimate of size and nature of the market for a practicable method: a review designed for technology transfer.

ATP is the energy currency of cells. ATP depletion is a central process in pathogenesis, in particular ischaemia, hypoxia and hypoglycaemia. ATP depletion in cells can be indirectly measured from the increased concentrations of extracellular hypoxanthine, a central intermediate in the metabolism of ATP. Cell damage secondary to ATP depletion can also be measured from extracellular hypoxanthine. The relevant biochemistry and physiology is briefly reviewed. Since market size is needed for investment decisions that would allow technology transfer, the numbers of hypoxanthine analyses that are clinically justified from the extensive published evidence are calculated per million population from UK, Norwegian and other evidence. The concentration of oxygen in blood is measured to estimate whether mitochondrial oxidative phosphorylation is adequate. Measurements of bicarbonate are used to estimate anaerobic glycolysis. Since the indirect estimation of ATP depletion is a major objective of blood gas and acid-base analyses, the number of such analyses per million population provides a good estimate of potential market size for a more direct method of estimating ATP depletion. A method is required for the rapid, dispersed emergency analyses needed clinically. Routes for method development are indicated. Competition, risks, acceptability, consumer motivation and timetables are indicated for the development phase. There are medicolegal pressures, especially in the USA, for the proposed advances to be widely used.

Adenosine Triphosphate↗

PubMed1996

Mechanisms of tissue injury by oxygen radicals: implications for neonatal disease.

A role of the oxygen radical generating system hypoxanthine-xanthine oxidase in hypoxia-reoxygenation injury was proposed 15 years ago. In recent years, however, new understanding of hypoxia-reoxygenation injury has been achieved and the significance of other oxygen radical generating systems has been acknowledged too. The hypothesis that an oxygen radical disease exists in preterm infants has recently been strengthened; an important observation is that preterm infants have lower activities of erythrocyte Cu/Zn superoxide dismutase compared to term babies. New actions of oxygen radicals have also been emphasized, and recently it has been demonstrated that the degree of protein oxidation of the lung of newborn infants is associated with chronic lung injury. The new insight into the interaction of oxygen radicals with other systems as excitatory amino acids and the NO system also increases the possibility to understand and hence prevent oxygen radical injury in the preterm infant as well as in adults exposed to an increased load of oxygen radicals.

Bronchopulmonary Dysplasia↗

PubMed1996

Hemodynamics and tissue blood flow after porcine surfactant replacement in surfactant-depleted newborn piglets.

In 22 newborn piglets we studied the effect of hypovolemia or hypoxemia on hemodynamics and regional blood flow after instillation of porcine surfactant. Surfactant deficiency was obtained by repeated lung lavage, and blood flow measurements were carried out using radioactive microspheres. Three groups of piglets were studied, controls (n = 8), hypovolemia (n = 7), and hypoxemia (n = 7). Three to five minutes after instillation of surfactant, mean arterial blood pressure decreased significantly in all three groups with a mean decrease (+/- SD) of 31(+/- 12), 33(+/- 9), and 29(+/- 9) mm Hg, respectively (p < 0.01 in all three groups). Systemic vascular resistance decreased significantly in all three groups immediately after surfactant instillation (p < 0.01) and returned to presurfactant level after 60 min. Blood flow did not change after surfactant instillation in any of the three groups, in neither skin, muscle, pancreas, brain, nor retina. In liver, kidney, intestine, and choroidea there was a decrease in blood flow immediately after instillation with return to presur-factant levels within 60 min. Hypoxemia or hypovolemia before surfactant instillation did not increase the hemodynamic instability. The decrease in mean arterial blood pressure was caused by a vasodilation and not by a reduced cardiac output.

Animals↗

PubMed1996

Regional blood flow during severe hypoxemia and resuscitation with 21% or 100% O2 in newborn pigs.

Our aim was to determine whether the use of room air or 100% oxygen has different effects on the peripheral circulation during resuscitation from severe hypoxemia. Twenty-four piglets, 2-to 5-days old, were anesthetized with pentobarbital and randomized to control (n = 5, surgery only) or hypoxemia. Hypoxemia (FiO2 = 0.08) was continued until base excess reached - 20 mml/L. Resuscitation was then performed with 21% (n = 10) or 100% O2 (n = 9) for 25 min followed by 21% O2 in both groups. Regional blood flow was measured with radioactive microspheres. Both hypoxic groups showed marked hyperemia during resuscitation in cardiac and skeletal muscle, a moderate hyperemia in intestine and pancreas while kidneys, liver, spleen and skin showed no hyperemic response. There were no significant differences between the two treatment groups in blood flow to any organ. Arterial oxygen content was significantly higher in the 100% O2 group than in the 21% O2 at 5 and 20 min after onset of resuscitation (11.6 +/- 0.7 and 11.2 +/- 0.6 vs 8.6 +/- 0.3 and 8.7 +/- 0.3 ml/100 ml, p < 0.01). Oxygen delivery was, however, significantly higher in the 100% O2 group than in the 21% O2 group only to the intestine and pancreas at 5 min of resuscitation. We conclude that resuscitation with 21% or 100% oxygen produces similar changes in peripheral blood flow in this porcine model of neonatal hypoxemia.

Animals↗

PubMed1996

Beta-endorphin immunoreactivity levels in CSF after laryngeal chemoreflex activation correlate with apnoea duration in piglets.

UNLABELLED: The activation of the laryngeal chemoreflex may be a pathogenic mechanism in apnoea, apparent life threatening events, and SIDS. Infants with apnoea and increased levels of beta-endorphin immunoreactivity in CSF have been successfully treated with naloxone. Beta-endorphin may induce respiratory depression, and naloxone is a beta-endorphin antagonist. We therefore wanted to measure beta-endorphin levels in CSF before and after the chemoreflex induced apnoea. This study includes 13 piglets, 5-10 days of age, treated with and without naloxone. Respiration, blood pressure, and heart rate were monitored. CSF was sampled before and after the laryngeal chemoreflex induced apnoea. We found a shorter duration of apnoea in the piglets which had received naloxone than in those which did not (p = 0.02). The beta-endorphin immunoreactivity levels in CSF increased after apnoea, and the increased levels correlated positively with the duration of the apnoea in the piglets which had not received naloxone (r = 0.94, p = 0.02), but not in those pretreated with naloxone (r = 0.1, p = 0.8). The median amount of beta-endorphin immunoreactivity in CSF after apnoea in the naloxone-treated piglets was not significantly different from that in the non-treated piglets: 615 +/- 589 (n = 7) fmol/ml CSF and 984 +/- 851 (n = 6) fmol/ml CSF, respectively. The beta-endorphin immunoreactivity levels measured before the apnoea were less than 4.3 fmol/ml CSF. CONCLUSION: The laryngeal chemoreflex induced apnoea may possible be partly mediated by beta-endorphin.

Animals↗

PubMed1996

Role of xanthine oxidase and its inhibitor in hypoxia: reoxygenation injury.

OBJECTIVE: This article reviews the biochemistry and function of xanthine dehydrogenase (XDH) and xanthine oxidase (XO) as well as their role in hypoxia-reoxygenation injury. Possible benefits of XO blockade are discussed. METHODOLOGY: The available literature was reviewed. RESULTS: It is evident that relatively high activities of XO are restricted to a few organs in man. Because positive effects of XO blockade with allopurinol have been reported even in organs containing relatively low activities of XO, two other possible favorable actions of allopurinol are mentioned. First it may act as an oxygen radical scavenger, and second, it may augment the adenine nucleotides and, hence, adenosine triphosphate concentration in the cell. CONCLUSIONS: XDH and XO may play an important role in a series of pathophysiologic conditions. Their role in hypoxia-reoxygenation injury has been critically reviewed. However, care should be exercised in starting randomized trials to prevent hypoxia-reoxygenation injury with allopurinol, especially in newborn infants. SPECULATION: XDH and XO are released from the liver during hypoxic conditions, for instance, and consequently, they may reach a number of organs via the circulation.

Animals↗