Comparison of Short- and Long-Duration Oxygen Treatment after Cerebral Asphyxia in Newborn Piglets

Solås, Anne-Beate; Munkeby, Berit H.; Saugstad, Ola Didrik

doi:10.1203/01.pdr.0000128978.90201.1d

Cited by 31 publications

(17 citation statements)

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“…Similarly, in other studies, the duration of postischemic reoxygenation with use of pure oxygen varies from 5 min to 24 h regardless of the resuscitation-induced changes in CBF (4,5,25). This may limit the clinical value of experimental data.…”

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confidence: 95%

“…To date, results of these studies are conflicting. For instance, it was reported that in asphyxiated pigs the Re-O 2 restored CBF significantly faster and more complete compared with Re-Air (4). Significantly higher levels of excitatory amino acids were found in the striatum of newborn HI-piglets Re-Air compared with Re-O 2 piglets which may be indicative of less favorable neurologic prognosis for Re-Air animals (5).…”

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confidence: 99%

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Reoxygenation with 100% Oxygen Versus Room Air: Late Neuroanatomical and Neurofunctional Outcome in Neonatal Mice with Hypoxic-Ischemic Brain Injury

et al. 2006

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Study investigated neuroutcome in mice subjected at 7-8 d of life to hypoxic-ischemic brain injury (HI) followed by 30 min of reoxygenation with 100% O 2 (Re-O 2 ) or room air (Re-Air). At 24 h of recovery, mouse reflexes were tested. At 7 wks after HI spatial orientation and memory were assessed in the same mice. Mortality rate was recorded at 24 h and at 7 wks of recovery. In separate cohort of mice, changes in cerebral blood flow (CBF) during HI-insult and reoxygenation were recorded. T he resuscitation of asphyxiated neonates is aimed to reestablish tissue oxygen delivery by restoring blood flow and increasing the arterial oxygen content. Use of 100% O 2 during neonatal resuscitation is currently recommended (1). However, Re-O 2 compared with Re-Air significantly exacerbates an oxidative stress in asphyxiated neonates (2), which is one of the mechanisms of HI-brain injury (3). To avoid hyperoxia-induced oxidative stress, the efficacy of resuscitation with room air (RA) instead of 100% O 2 is being extensively studied. To date, results of these studies are conflicting. For instance, it was reported that in asphyxiated pigs the Re-O 2 restored CBF significantly faster and more complete compared with Re-Air (4). Significantly higher levels of excitatory amino acids were found in the striatum of newborn HI-piglets Re-Air compared with Re-O 2 piglets which may be indicative of less favorable neurologic prognosis for Re-Air animals (5). However, Liu. Y and co-authors, using a canine model of cardiac arrest, demonstrated that Re-O 2 versus ReAir resulted in greater neurologic impairment assessed at 24 h of recovery (6). In contrast, the postischemic use of hyperbaric oxygenation, which produces substantial oxidative stress (7), significantly improved neurologic score following focal cerebral ischemia in adult rats and HI in neonatal rats (8,9). Hyperbaric oxygenation used as a mode of resuscitation from experimental heatstroke in rats was shown to be significantly neuroprotective (10). Meier and co-authors reported that hyperoxic ventilation significantly reduced short-term (6 h) mortality due to systemic ischemia following an acute hemorrhagic shock in pigs (11). The most recent meta-analysis indicates that there are not enough data to challenge current recommendation of using of pure O 2 during resuscitation (12).The assessment of long-term neurologic handicap following HI is of paramount clinical value to define the ultimate efficacy of Re-O2 versus Re-Air in an asphyxiated subject. There are no reports on late neurologic outcome and reoxygenation strategy following asphyxia. This work was undertaken to provide experimental data on short-and long-term neuropathological and neurofunctional outcomes in HIaffected mice re-oxygenated with either 100% O 2 or RA immediately following the index event. MATERIALS AND METHODSMurine model of HI. Three day old (p3) C57/BL6J mice of both genders were purchased from Jackson Laboratories (Bar Harbor, ME) with their birth mothers. All research was conducted according ...

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Reoxygenation with 100% Oxygen Versus Room Air: Late Neuroanatomical and Neurofunctional Outcome in Neonatal Mice with Hypoxic-Ischemic Brain Injury

et al. 2006

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“…Research in animal (Herpin et al, 2001;MotaRojas et al, 2005a,b;2006a,b) and human perinatology (Randall et al, 1979;Tollofsrud et al, 2001;Solas et al, 2004) have used sows' foetuses and newborns as experimental animal models (Gonzalez-Lozano et al, 2009a,b;Olmos-Hernandez et al, 2008), because this species has shown similarities to human medicine in terms of changes in energy metabolism during normal and pathological childbirth. Foetal growth is a complex process that involves the interaction of mother, placenta and foetus.…”

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Foetal and neonatal energy metabolism in pigs and humans: a review

Mota-Rojas¹,

Orozco-Gregorio²,

Villanueva-García³

et al. 2011

Vet. Med. - Czech

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ABSTRACT:The aim of this review was to elaborate a conceptual framework of the most important aspects of the main biochemical processes of synthesis and breakdown of energy substrates that human and pig foetuses and newborns can use during the transition from foetus to newborn. Under normal physiological conditions, the growth and development of the foetus depends upon nutrients such as glucose, lipids and amino acids. In addition to the maternal and foetal status, genetic factors are also reported to play a role. The main function of the placenta in all species is to promote the selective transport of nutrients and waste products between mother and foetus. This transport is facilitated by the close proximity of the maternal and foetal vascular systems in the placenta. The foetus depends on the placental supply of nutrients, which regulates energy reserves by means of glycogen storage. Also, the synthesis of foetal hepatic glycogen guarantees energy reserves during perinatal asphyxia or maternal hypoglycaemia. However, the foetus can also obtain energy from other resources, such as gluconeogenesis from the intermediary metabolism of the Krebs cycle and most amino acids. Later, when the placental glucose contribution ends during the transition to the postnatal period, the maturation of biological systems and essential metabolic adaptations for survival and growth is required. The maintenance of normoglycaemia depends on the conditions that determine nutrient status throughout life: the adequacy of glycogen stores, the maturation of the glycogenolytic and gluconeogenic pathway, and an integrated endocrine response.

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“…Australia, Canada, Finland, the Netherlands, Sweden, and the United Kingdom recommend initial ventilation with air, because of the results from several experimental (2)(3)(4)(5) and clinical (6 -13) studies indicating that resuscitation with 100% oxygen is harmful. In the clinical studies, the time of exposure to 100% oxygen was typically 5-7 min (8,13), whereas only one animal study (5) has investigated an exposure time to oxygen less than 15 min.…”

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High Brain Tissue Oxygen Tension During Ventilation With 100% Oxygen After Fetal Asphyxia in Newborn Sheep

et al. 2009

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ABSTRACT:The optimal inhaled oxygen fraction for newborn resuscitation is still not settled. We hypothesized that short-lasting oxygen ventilation after intrauterine asphyxia would not cause arterial or cerebral hyperoxia, and therefore be innocuous. The umbilical cord of fetal sheep was clamped and 10 min later, after delivery, ventilation with air (n ϭ 7) or with 100% oxygen for 3 (n ϭ 6) or 30 min (n ϭ 5), followed by air, was started. Among the 11 lambs given 100% oxygen, oxygen tension (P O2 ) was 10.7 (1.8 -56) kPa [median (range)] in arterial samples taken after 2.5 min of ventilation. In those ventilated with 100% oxygen for 30 min, brain tissue P O2 (Pbt O2 ) increased from less than 0.1 kPa in each lamb to individual maxima of 56 (30 -61) kPa, whereas in those given oxygen for just 3 min, Pbt O2 peaked at 4.2 (2.9 -46) kPa. The maximal Pbt O2 in airventilated lambs was 2.9 (0.8 -5.4) kPa. Heart rate and blood pressure increased equally fast in the three groups. Thus, prolonged ventilation with 100% oxygen caused an increase in Pbt O2 of a magnitude previously only reported under hyperbaric conditions. Reducing the time of 100% oxygen ventilation to 3 min did not consistently avert systemic hyperoxia. (Pediatr Res 65: 57-61, 2009) C urrent guidelines from the International Liaison Committee on Resuscitation breathe considerable uncertainty as to how much supplementary oxygen should be given during resuscitation of newborn asphyxiated infants (1). Previous recommendations were to be generous with oxygen, but recent guidelines from a number of countries, e.g. Australia, Canada, Finland, the Netherlands, Sweden, and the United Kingdom recommend initial ventilation with air, because of the results from several experimental (2-5) and clinical (6 -13) studies indicating that resuscitation with 100% oxygen is harmful. In the clinical studies, the time of exposure to 100% oxygen was typically 5-7 min (8,13), whereas only one animal study (5) has investigated an exposure time to oxygen less than 15 min.We speculated that very short times of exposure might not allow systemic hyperoxia to develop and so be harmless to the newborn infant, except for a possible negative effect on the lungs. In fact, the pulse oximetric saturation at 3 min after birth is usually below 80% (14,15) in the normal air-breathing infant, suggesting the presence of cardiac or pulmonary rightto-left shunts. One might expect that such shunts would delay the appearance of arterial hyperoxemia in the infant breathing pure oxygen. However, this has been studied neither in normal nor in asphyxiated subjects.We used a sheep model of term intrauterine asphyxia with postnatal resuscitation, and hypothesized that hyperoxia of arterial blood and of brain tissue could be prevented by limiting the period of ventilation with 100% oxygen to 3 min. We also investigated whether the speed of circulatory recovery, as reflected by the heart rate (HR) and mean arterial blood pressure (MAP) responses, and the speed of recovery of brain oxygenation, as reflected ...

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Comparison of Short- and Long-Duration Oxygen Treatment after Cerebral Asphyxia in Newborn Piglets

Cited by 31 publications

References 33 publications

Reoxygenation with 100% Oxygen Versus Room Air: Late Neuroanatomical and Neurofunctional Outcome in Neonatal Mice with Hypoxic-Ischemic Brain Injury

Reoxygenation with 100% Oxygen Versus Room Air: Late Neuroanatomical and Neurofunctional Outcome in Neonatal Mice with Hypoxic-Ischemic Brain Injury

Foetal and neonatal energy metabolism in pigs and humans: a review

High Brain Tissue Oxygen Tension During Ventilation With 100% Oxygen After Fetal Asphyxia in Newborn Sheep

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