Early cerebral metabolic and electrophysiological recovery during controlled hypoxemic resuscitation in piglets

Feet, Björn Aage; Brun, Nikolai C.; Hellström‐Westas, Lena; Svenningsen, Nils W.; Greisen, Gorm; Saugstad, Ola Didrik

doi:10.1152/jappl.1998.84.4.1208

Cited by 32 publications

(12 citation statements)

References 34 publications

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“…Two laser Doppler probes were implanted into the cerebral cortex (16 mm anterior, 5 mm lateral to the bregma and 4 mm vertical from the surface of the cortex, one probe on each side). The coordinates for the cerebral striatum and cortex have been verified through neuropathological postmortem examination in earlier studies [9].…”

Section: Animal Preparationmentioning

confidence: 99%

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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Section: Animal Preparationmentioning

confidence: 99%

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

Solås

Kalous²,

Saugstad³

2004

Neonatology

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“…The piglet model of neonatal hypoxia-ischaemia is widely used for the study of this condition (Björkman et al, 2006;Borke et al, 2004;Feet et al, 1998;Khurana et al, 2002;Laptook et al, 1994;O'Brien et al, 2006;Park et al, 2001;Thoresen et al, 2001) and many studies require a means of comparing the severity of neural injury between animals. Previous studies by this group and others have used histological examination of the brain 72 h after hypoxia to assess the extent of neural injury (Foster et al, 2001;Gunn et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

MAP2 provides reliable early assessment of neural injury in the newborn piglet model of birth asphyxia

Lingwood

Healy

Sullivan

et al. 2008

Journal of Neuroscience Methods

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“…In a piglet model of hypoxic-ischemic brain injury in newborns, striatal neuron necrosis evolves rapidly (33). We have investigated changes in corpus striatum in a global hypoxia piglet model, imitating birth asphyxia, as in several of our earlier studies (34,35). Especially the cerebral ischemia after a hypoxiainduced myocardial failure is most harmful (36) because permitting the mean arterial blood pressure (MABP) to fall to 15 mm Hg also induces cerebral perfusion disturbances.…”

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confidence: 99%

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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Early cerebral metabolic and electrophysiological recovery during controlled hypoxemic resuscitation in piglets

Cited by 32 publications

References 34 publications

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

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

MAP2 provides reliable early assessment of neural injury in the newborn piglet model of birth asphyxia

Resuscitation with 100% O2 Increases Cerebral Injury in Hypoxemic Piglets

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