Cerebral hypoxemia-ischemia and reoxygenation with 21% or 100% oxygen in newborn piglets: Effects on extracellular levels of excitatory amino acids and microcirculation

Solås, Anne-Beate; Kutzsche, Stefan; Vinje, Morten Larsen; Saugstad, Ola Didrik

doi:10.1097/00130478-200110000-00011

Cited by 62 publications

(36 citation statements)

References 29 publications

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“…14,15 There is evidence in newborn animal models of asphyxia that exposure to high concentrations of oxygen at resuscitation does not confer any clinical advantage and is potentially harmful at the cellular level. 16,17 Two animal models of hypoxia-ischemia and persistent bradycardia found that those resuscitated with room air rather than 100% oxygen developed untoward biochemical changes in the brain (LOE 5 18,19 ).…”

Section: Consensus On Sciencementioning

confidence: 99%

Part 11: Neonatal Resuscitation

Perlman¹,

Wyllie²,

Kattwinkel³

et al. 2010

Circulation

561

358

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Section: Consensus On Sciencementioning

confidence: 99%

Part 11: Neonatal Resuscitation

Perlman¹,

Wyllie²,

Kattwinkel³

et al. 2010

Circulation

561

358

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“…The amino acid content was determined by high-performance liquid chromatography (Perkin Elmer, Norwalk, Conn., USA) by a method modified from Lindroth and Mopper [10], as previously described [7]. Due to technical problems with the analyzer, amino acid measurements had to be excluded in 4 animals (2 in each group).…”

Section: Analysis Of Amino Acidsmentioning

confidence: 99%

“…Measurements of changes in cerebral cortical microcirculation were performed with a two-channel laser Doppler flowmeter (Periflux 4001 Master, Perimed AB, Stockholm, Sweden) as previously described [7].…”

Section: Laser Doppler Flowmetrymentioning

confidence: 99%

“…In a piglet model of global hypoxemia, no significant differences in mean arterial blood pressure (MABP), base deficit, hypoxanthine in plasma, brain morphology, cerebral blood flow or extracellular levels of hypoxanthine and excitatory amino acids in the brain had been found after reoxygenation with 21% O 2 compared with 100% O 2 [1][2][3][4]. However, in a recent study, we have changed our experimental model of asphyxia in newborn piglets from global hypoxemia to combined cerebral hypoxemia-ischemia (HI) [7]. In that study, we found significantly lower MABP (25%), significantly higher levels of extracellular excitatory amino acids in the striatum, and a significantly greater degree of hypoperfusion (45%) in the cerebral cortex after initial reoxygenation with 21% compared with 100% O 2 .…”

Section: Introductionmentioning

confidence: 99%

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Reoxygenation with 100 or 21% Oxygen after Cerebral Hypoxemia-Ischemia-Hypercapnia in Newborn Piglets

Solås

Kalous²,

Saugstad³

2004

Neonatology

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We tested if reoxygenation with 100% O₂ was superior to 21% O₂ after combined cerebral hypoxemia-ischemia-hypercapnia (HIH) in newborn piglets. Twenty-eight piglets were randomized to reoxygenation with 100 or 21% O₂ following asphyxia. Asphyxia was induced by ventilation with 8% O₂, adding CO₂, and temporary occlusion of both common carotid arteries. After 20 min, reoxygenation-reperfusion was started with 21% O₂ (HIH 21% group, n = 13) or 100% O₂ (HIH 100% group, n = 11) for 30 min followed by 21% O₂. All piglets were observed for 2 h. We measured mean arterial blood pressure (MABP), changes in microcirculation in the cerebral cortex (laser Doppler), and extracellular concentrations of hypoxanthine in the cortex and amino acids in the striatum (microdialysis). We found significantly higher MABP and better restoration of microcirculation after reoxygenation with 100% compared with 21% O₂, but no differences in biochemical markers were found between the groups. This indicates that the brain tolerated reoxygenation with 21% as well as with 100% O₂ in the present model of experimental asphyxia in spite of the differences in MABP and cerebral microcirculation.

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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.…”

mentioning

confidence: 95%

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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Cerebral hypoxemia-ischemia and reoxygenation with 21% or 100% oxygen in newborn piglets: Effects on extracellular levels of excitatory amino acids and microcirculation

Cited by 62 publications

References 29 publications

Part 11: Neonatal Resuscitation

Part 11: Neonatal Resuscitation

Reoxygenation with 100 or 21% Oxygen after Cerebral Hypoxemia-Ischemia-Hypercapnia in Newborn Piglets

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

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