Hypoxemia and Reoxygenation with 21% or 100% Oxygen in Newborn Pigs: Changes in Blood Pressure, Base Deficit, and Hypoxanthine and Brain Morphology

Rootwelt, Terje; Løberg, Else Marit; Møen, Atle; Øyasæter, Stephanie; Saugstad, Ola Didrik

doi:10.1203/00006450-199207000-00021

Cited by 105 publications

(51 citation statements)

References 15 publications

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“…All values are given as mean Ϯ SEM. 788 between 21 and 100% oxygen even 4 d after hypoxia (54). Despite this, our study indicates the importance of adjusting down the oxygen level during resuscitation after global hypoxia.…”

Section: Discussionmentioning

confidence: 59%

Resuscitation with 100% O2 Increases Cerebral Injury in Hypoxemic Piglets

Munkeby

Børke

Björnland³

et al. 2004

Pediatr Res

120

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Perinatal asphyxia is a major cause of immediate and postponed brain injury in the newborn. We hypothesized that resuscitation with 100% O 2 compared with ambient air is detrimental to the cerebral tissue. We assessed cerebral injury in newborn piglets that underwent global hypoxia and subsequent resuscitation with 21 or 100% O 2 by extracellular glycerol, matrix metalloproteinase (MMP) expression levels, and oxidative stress. Extracellular glycerol was sampled by cerebral microdialysis. MMP levels were analyzed in cerebral tissue by gelatin zymography, broad matrix degrading capacity, and real-time PCR. Total endogenous antioxidant capacity was measured by the oxygen radical absorbance capacity assay. Extracellular glycerol increased 50% after resuscitation with 100% O 2 compared with 21% O 2 . Total MMP activity was doubled in resuscitated animals at endpoint compared with baseline (p ϭ 0.018), and the MMP-2 activity was significantly increased in piglets that were resuscitated with 21% O 2 (p ϭ 0.003) and 100% O 2 (p ϭ 0.001) compared with baseline. MMP-2 mRNA level was 100% increased in piglets that were resuscitated with 100% O 2 as compared with 21% O 2 (p Ͻ 0.05). Oxygen radical absorbance capacity values in piglets that were resuscitated with 100% O 2 were considerably reduced compared with both baseline (p ϭ 0.001) and piglets that were resuscitated with 21% O 2 (p ϭ 0.001). In conclusion, our data show increased MMP-2 activity at both gene and protein levels, accompanied with cerebral leakage of glycerol, presumably triggered by augmented oxidative stress. Traditionally, asphyxiated newborn infants have been resuscitated using 100% oxygen in the delivery room (1). However, clinical trials have shown that room air is as efficient as pure oxygen in securing the survival of asphyxiated newborn infants (2-5). Therefore there is an ongoing debate whether to use ambient air or 100% O 2 in neonatal resuscitation (6 -9).Hyperoxia followed by reoxygenation is thought to increase the production of reactive oxygen species and disrupt the antioxidant mechanisms (10). Elevated oxidative stress can directly influence the cell cycle and additionally alter a number of significant cell functions, such as signal transduction, DNA and RNA synthesis, protein synthesis, and enzyme activation (11,12). Furthermore, hypoxic-ischemic injury and reactive oxygen species are found to trigger inflammation in the immature brain (13).Interstitial glycerol is a sensitive and reliable marker of cell damage in experimental cerebral ischemia (14 -16). Degradation of membrane phospholipids is a well-known phenomenon in acute brain injuries and is thought to underlie the disturbance of vital cellular membrane functions.Matrix metalloproteinases (MMPs) are a family of Ͼ20 zinc-and calcium-dependent endopeptidases that are involved in the remodeling of the extracellular matrix (ECM) in a variety of physiologic and pathologic conditions (17

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Section: Discussionmentioning

confidence: 59%

Resuscitation with 100% O2 Increases Cerebral Injury in Hypoxemic Piglets

Munkeby

Børke

Björnland³

et al. 2004

Pediatr Res

120

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“…In the presence of elevated levels of cerebral hypoxanthine and xanthine, a large amount of oxygen administered during resuscitation after peripartal asphyxia may provide adverse effects. In newborn pigs, resuscitation after asphyxia with 100% oxygen was not shown to be beneficial compared with resuscitation with 21% oxygen (20). It may therefore be worthwhile to consider using 21% instead of 100% oxygen during resuscitation after peripartal asphyxia.…”

Section: --30mentioning

confidence: 99%

Effects of Surgery and Asphyxia on Levels of Nucleosides, Purine Bases, and Lactate in Cerebrospinal Fluid of Fetal Lambs

et al. 1994

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During severe oxygen shortage, the fetal brain resorts to anaerobic metabolism and ATP becomes catabolized. High levels of nucleosides, hypoxanthine, and xanthine (ATP catabolites) in cerebrospinal fluid (CSF) may therefore be associated with increased neonatal neurologic morbidity. In 22 fetal lambs (3 to 5 d after surgery, gestational age 123.5 r 3.5 d), arterial oxygen content was progressively reduced to 35% of the baseline value with a balloon occluder around the maternal common internal iliac artery. This resulted in a 1-h period of asphyxia, leading to a pH of 7.02 ? 0.03 and a base excess of -17.0 ? 1.0 mM. Mortality was 50%. CSF was sampled from the spinal cistern and analyzed using HPLC. During reoxygenation, hypoxanthine and xanthine may serve as substrate for xanthine oxidase with concomitant production of oxygen-derived free radicals, which may aggravate cerebral damage. The main difference between surviving and nonsurviving animals was the speed of increment of ATP catabolites in CSF: in the surviving group levels increased steadily, recovery values being significantly elevated compared with asphyxia values, whereas in the nonsurviving group the rise was rapid and levels during asphyxia did not differ significantly from levels during recovery. We conclude that I ) catheterization of the spinal cistern leads to increased levels of CSF hypoxanthine, xanthine, and inosine, and 2) during fetal asphyxia, levels of these ATP catabolites and lactate in CSF increase. 3 ) Maximum levels are reached during the recovery period and are similar for surviving and nonsurviving animals, but during asphyxia CSF levels of hypoxanthine and lactate were higher in the nonsurviving fetuses. 4) The rate of increase of ATP catabolites in CSF is higher in the nonsurviving animals and may therefore be predictive for fetal death. (1) and preferential streaming of well-oxygenated blood in the heart (2), the fetal cerebrum is provided with as much oxygen as possible. During severe or sustained oxygen shortage, however, the brain too resorts to anaerobic metabolism. Lack of oxygen impairs mitochondria1 functioning, leading to energy shortage (3); ATP becomes degraded to AMP and, after dephosphorylation, further to adenosine, inosine, and hypoxanthine. Serum levels of hypoxanthine are considered a sensitive indicator of the hypoxic insult (4). Moreover, formation of hypoxanthine and xanthine may aggravate outcome after such an insult, because during reoxygenation hypoxanthine and xan-

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“…In this and a series of subsequent experiments, we confirmed that 21% oxygen is as efficient as 100% oxygen for resuscitation. [10][11][12][13][14][15][16] The findings in the newborn piglet were consistent, and I realized that the time had come to test our hypothesis in a clinical study. Siddarth Ramji in New Delhi immediately agreed to participate, and the pilot clinical trial was carried out in India, enrolling 84 newborn infants randomized to room air or 100% oxygen resuscitation.…”

Section: Discovery Through a Failurementioning

confidence: 73%

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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Hypoxemia and Reoxygenation with 21% or 100% Oxygen in Newborn Pigs: Changes in Blood Pressure, Base Deficit, and Hypoxanthine and Brain Morphology

Cited by 105 publications

References 15 publications

Resuscitation with 100% O2 Increases Cerebral Injury in Hypoxemic Piglets

Resuscitation with 100% O2 Increases Cerebral Injury in Hypoxemic Piglets

Effects of Surgery and Asphyxia on Levels of Nucleosides, Purine Bases, and Lactate in Cerebrospinal Fluid of Fetal Lambs

Why are we still using oxygen to resuscitate term infants?

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