Resuscitation of Hypoxic Newborn Piglets With Supplementary Oxygen Induces Dose-Dependent Increase in Matrix Metalloproteinase-Activity and Down-Regulates Vital Genes

Solberg, Rønnaug; Andresen, Jannicke H; Pettersen, Solveig; Wright, Marianne; Munkeby, Berit H.; Charrat, Eliane; Khrestchatisky, Michel; Rivera, Santiago; Saugstad, Ola Didrik

doi:10.1203/pdr.0b013e3181cde843

Cited by 12 publications

(21 citation statements)

References 42 publications

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“…In our newborn hypoxia-reoxygenation piglet model, matrix metalloproteinases (MMP) 2 and 9 were measured to assess oxidative tissue damage and repair in lung, liver, heart and brain. Resuscitation with 100% oxygen gave significantly higher values compared with ambient air [34,35,37,38]. Studies in newborn lambs also showed more injury to the brain when resuscitation was carried out with 100% oxygen compared with air [39].…”

Section: Hyperoxic Injurymentioning

confidence: 99%

“…Using different oxygen concentrations for newborn resuscitation in a newborn piglet model, we found a clear dose-dependent oxygen toxicity [35,38,40] as shown in figure 2. In brain tissue, the most prominent changes occurred in neuronal populations in a dose-response manner.…”

Section: Hyperoxic Injurymentioning

confidence: 99%

“…Oxygen vs. dose dependency: dose-dependent hyperoxic injury (adapted from Solberg et al [37,38,40]). The graph visualizes how different parameters have a dose-dependent relative change according to the amount of oxygen used for resuscitation.…”

Section: Hyperoxic Injurymentioning

confidence: 99%

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Oxygenation of the Newborn: A Molecular Approach

Saugstad

Sejersted²,

Solberg³

et al. 2012

Neonatology

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In this review oxygenation and hyperoxic injury of newborn infants are described through molecular and genetic levels. Protection and repair mechanisms that may be important for a new understanding of oxidative stress in the newborn are discussed. The research summarized in this article represents a basis for the reduced oxygen supplementation and oxidative load of newborn babies, especially since the turn of the century. The mechanisms discussed may also contribute to an understanding of why hyperoxic resuscitation of the newborn may damage DNA and affect its repair, thus increasing the risk that it may be carcinogenic. Today, term babies should be resuscitated with air rather than 100% oxygen and very and extremely low birth weight infants in need of stabilization or resuscitation at birth should be administered initially 21–30% oxygen and the level should be titrated according to the response, preferably measured by pulse oximetry. In the postnatal period the oxygen saturation should be targeted low <95%; however, saturations between 85 and 89% seem to increase mortality. The optimal oxygen saturation target for these infants postnatally is still unknown.

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Section: Hyperoxic Injurymentioning

confidence: 99%

Section: Hyperoxic Injurymentioning

confidence: 99%

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Oxygenation of the Newborn: A Molecular Approach

Saugstad

Sejersted²,

Solberg³

et al. 2012

Neonatology

Self Cite

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show abstract

“…19 Subsequent experimental studies and clinical studies by Max Vento and his group and others have been extremely important, as these studies presented evidence that it is actually harmful to resuscitate newborn babies with 100% oxygen. [20][21][22][23][24][25][26] The Resair 2 study was criticized mainly for two reasons. First, the study was not strictly randomized nor was it blinded.…”

Section: Discovery Through a Failurementioning

confidence: 99%

“…This is in agreement with the findings of numerous animal experiments showing that a brief exposure of oxygen following hypoxia has dramatic deleterious effects on the newborn brain. 20,21,24,25 It has been shown that the first breath is delayed by 30 s in babies resuscitated with 100% compared with those resuscitated with 21% oxygen. Heart rate at 90 s and the 5-m Apgar score were also lower when 100% oxygen was applied.…”

Section: Discovery Through a Failurementioning

confidence: 99%

Why are we still using oxygen to resuscitate term infants?

Saugstad

2010

J Perinatol

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This article summarizes the historical background for the use of oxygen during newborn resuscitation and describes some of the research and the process of changing the previous practice from a high-to a low-oxygen approach. Findings of a recent Cochrane review suggest that more than 100 000 newborn lives might be saved globally each year by changing from 100 to 21% oxygen for newborn resuscitation. This estimate represents one of the largest yields for a simple therapeutic approach to decrease neonatal mortality in the history of pediatric research. Available data also suggest that, for the very low birth weight infant, use of the low-oxygen approach should be considered with the understanding that some of the smallest and sickest preterm neonates will need some level of oxygen supplementation during the first minutes of postnatal life. As more data are needed for the very preterm population, creation of strict guidelines for these infants would be premature at present. However, it can be stated that term and late preterm infants in need of resuscitation should, in general, be started on 21% oxygen, and if resuscitation is not started with 21% oxygen, a blender should be available, enabling the administration of the lowest FiO 2 possible to keep heart rate and SaO 2 within the target range. For extremely low birth weight infants, initial FiO 2 could be between 0.21 and 0.30 and adjusted according to the response in SaO 2 and heart rate.

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Oxygen and oxidative stress in the perinatal period

et al. 2017

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Fetal life evolves in a hypoxic environment. Changes in the oxygen content in utero caused by conditions such as pre-eclampsia or type I diabetes or by oxygen supplementation to the mother lead to increased free radical production and correlate with perinatal outcomes.In the fetal-to-neonatal transition asphyxia is characterized by intermittent periods of hypoxia ischemia that may evolve to hypoxic ischemic encephalopathy associated with neurocognitive, motor, and neurosensorial impairment. Free radicals generated upon reoxygenation may notably increase brain damage. Hence, clinical trials have shown that the use of 100% oxygen given with positive pressure in the airways of the newborn infant during resuscitation causes more oxidative stress than using air, and increases mortality.Preterm infants are endowed with an immature lung and antioxidant system. Clinical stabilization of preterm infants after birth frequently requires positive pressure ventilation with a gas admixture that contains oxygen to achieve a normal heart rate and arterial oxygen saturation. In randomized controlled trials the use high oxygen concentrations (90% to 100%) has caused more oxidative stress and clinical complications that the use of lower oxygen concentrations (30–60%). A correlation between the amount of oxygen received during resuscitation and the level of biomarkers of oxidative stress and clinical outcomes was established. Thus, based on clinical outcomes and analytical results of oxidative stress biomarkers relevant changes were introduced in the resuscitation policies. However, it should be underscored that analysis of oxidative stress biomarkers in biofluids has only been used in experimental and clinical research but not in clinical routine. The complexity of the technical procedures, lack of automation, and cost of these determinations have hindered the routine use of biomarkers in the clinical setting. Overcoming these technical and economical difficulties constitutes a challenge for the immediate future since accurate evaluation of oxidative stress would contribute to improve the quality of care of our neonatal patients.

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Resuscitation of Hypoxic Newborn Piglets With Supplementary Oxygen Induces Dose-Dependent Increase in Matrix Metalloproteinase-Activity and Down-Regulates Vital Genes

Cited by 12 publications

References 42 publications

Oxygenation of the Newborn: A Molecular Approach

Oxygenation of the Newborn: A Molecular Approach

Why are we still using oxygen to resuscitate term infants?

Oxygen and oxidative stress in the perinatal period

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