Inflammation increases vulnerability to hypoxia in newborn piglets: Effect of reoxygenation with 21% and 100% O2

Lyng, Kristin; Braakhuis, Marjolein; Frøen, J. Frederik; Stray‐Pedersen, Babill; Saugstad, Ola Didrik

doi:10.1016/j.ajog.2004.11.058

Cited by 10 publications

(5 citation statements)

References 25 publications

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“…In contrast, Lyng et al (11) reported a peak Pbt O2 around only 5 kPa in piglets resuscitated with 100% oxygen for 30 min after a hypoxic injury with normal PaCO 2 . We believe that the discrepancies between the studies may largely be explained by the much higher PaCO 2 at the end of asphyxia in this study: 21 kPa (19 -23 kPa), and in the study of lambs (6).…”

Section: Discussionmentioning

confidence: 95%

Circulatory Recovery Is as Fast With Air Ventilation as With 100% Oxygen After Asphyxia-Induced Cardiac Arrest in Piglets

et al. 2009

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ABSTRACT:We investigated return of spontaneous circulation and of cerebral oxygenation after asphyxia-induced cardiac arrest, using ventilation with air, throughout, or with 100% oxygen for a shorter or longer period. Arterial pressure, heart rate, regional cerebral oxygen saturation (CrS O2 ), and brain tissue oxygen tension (Pbt O2 ) were measured in 1-d-old piglets that were hypoventilated with air and left in apnea until cardiac arrest. They were randomly assigned to be resuscitated with air (n ϭ 13), or with oxygen for 3 (n ϭ 12) or 30 min (n ϭ 13) and then with air. Nine, 10, and 10 animals, respectively, needed closed chest cardiac massage. One, none, and one, respectively, died. Median (quartile range) times from start of ventilation until heart rate reached 150 bpm were 67 (60 -76), 88 (76 -126), and 68 (56 -81) s. They were not significantly different, nor were the arterial pressure responses, times until CrS O2 reached 30%, or times until Pbt O2 had increased by 0.1 kPa from its nadir. Peak Pbt O2 values during resuscitation T he optimal fraction of inspired O 2 (FiO 2 ) for resuscitation of asphyxiated neonates is still not settled, although clinical and experimental evidences indicate that 21% is superior to 100% (1-4). In most of these studies, the time of exposure to pure oxygen exceeded 5 min, and it is unknown whether a very brief exposure to high FiO 2 at the start of resuscitation might improve myocardial oxygenation and hasten the return of adequate heart function without causing an organ damage.In three studies of experimental asphyxia (5-7), arterial pressure was restored as quickly by air ventilation as with 100% oxygen. However, few of the animals in these studies needed closed chest cardiac massage (CCCM), and the possibility remains that subjects with asphyxia, so severe that CCCM is needed, might be easier to resuscitate with a high FiO 2 . We tested this in 1-d-old piglets in cardiac arrest caused by severe asphyxia and hypothesized that ventilation with 100% oxygen would restore heart rate (HR) and arterial pressure faster than would ventilation with air. In addition, return of cerebral oxygenation was analyzed, by measuring regional oxygen saturation (CrS O2 ) and brain tissue oxygen tension (Pbt O2 ). The asphyxia was induced by hypoventilation followed by apnea to achieve the high blood PCO 2 levels that are characteristic of severe clinical perinatal asphyxia (8).Because the Pbt O2 is relevant to the question whether a high FiO 2 after asphyxia might cause brain damage, we extended the recording of brain oxygenation beyond the immediate resuscitation phase. Ventilation with 100% oxygen was limited to 3 min in some animals to see whether this could avoid cerebral hyperoxia. METHODSThis study was approved by the Animal Ethics Research Committee of Lund University. The animals were cared for and handled in accordance with European Guidelines for Use of Experimental Animals.Animal preparation. Thirty-eight domestic piglets (12-to 36-h old) were premedicated with intramuscular ketamin...

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Section: Discussionmentioning

confidence: 95%

Circulatory Recovery Is as Fast With Air Ventilation as With 100% Oxygen After Asphyxia-Induced Cardiac Arrest in Piglets

et al. 2009

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“…15%, in all animals. MAP decreased to a nadir of 14 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) mm Hg in 17 animals and to 32 mm Hg in one. HR decreased to 64 (30 -96) bpm.…”

Section: Resultsmentioning

confidence: 99%

“…The finding is probably due to a combination of factors, namely high Fi O2 , postischemic hyperemia accentuated by metabolic and respiratory arterial acidemia, and reduced metabolism (19) in the postasphyctic brain. Surprisingly, Lyng et al (20) found a much smaller peak Pbt O2 in 1-2-d-old piglets that were asphyxiated by breathing an hypoxic mixture and then resuscitated with 30 min of oxygen-ventilation. In these, Pbt O2 only increased to a maximum of approximately 5 kPa.…”

Section: Discussionmentioning

confidence: 99%

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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“…Deleterious interactions between the two major upstream mechanisms in pathogenesis of PVL, i.e., hypoxia‐ischemia and systemic infection/inflammation, may be mediated in considerable part by microglia. Thus, several studies of immature animals have demonstrated that pretreatment with the Gram‐negative bacterial product, LPS, at subthreshold doses (insufficient to cause brain injury), caused a subthreshold hypoxic‐ischemic insult to produce marked degrees of injury, including white matter injury (Eklind et al, 2001, 2004; Coumans et al, 2003; Lehnardt et al, 2003; Ikeda et al, 2004; Larouche et al, 2005; Wang et al, 2007a,b, 2009, 2010; Lyng et al, 2005; Rousset et al, 2008; Girard et al, 2009). In most of these experimental models the potentiation of hypoxic‐ischemic injury by LPS involved pretreatment several hours before the insult, although in one study LPS was administered many days before in utero .…”

Section: Pathogenesismentioning

confidence: 99%

The developing oligodendrocyte: key cellular target in brain injury in the premature infant

Volpe

Kinney

Jensen

et al. 2011

Intl J of Devlp Neuroscience

323

325

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Brain injury in the premature infant, a problem of enormous importance, is associated with a high risk of neurodevelopmental disability. The major type of injury involves cerebral white matter and the principal cellular target is the developing oligodendrocyte. The specific phase of the oligodendroglial lineage affected has been defined from study of both human brain and experimental models. This premyelinating cell (pre-OL) is vulnerable because of a series of maturation-dependent events. The pathogenesis of pre-OL injury relates to operation of two upstream mechanisms, hypoxia-ischemia and systemic infection/inflammation, both of which are common occurrences in premature infants. The focus of this review and of our research over the past 15-20 years has been the cellular and molecular bases for the maturation-dependent vulnerability of the pre-OL to the action of the two upstream mechanisms. Three downstream mechanisms have been identified, i.e., microglial activation, excitotoxicity and free radical attack. The work in both experimental models and human brain has identified a remarkable confluence of maturation-dependent factors that render the pre-OL so exquisitely vulnerable to these downstream mechanisms. Most importantly, elucidation of these factors has led to delineation of a series of potential therapeutic interventions, which in experimental models show marked protective properties. The critical next step, i.e., clinical trials in the living infant, is now on the horizon.

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Inflammation increases vulnerability to hypoxia in newborn piglets: Effect of reoxygenation with 21% and 100% O2

Cited by 10 publications

References 25 publications

Circulatory Recovery Is as Fast With Air Ventilation as With 100% Oxygen After Asphyxia-Induced Cardiac Arrest in Piglets

Circulatory Recovery Is as Fast With Air Ventilation as With 100% Oxygen After Asphyxia-Induced Cardiac Arrest in Piglets

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

The developing oligodendrocyte: key cellular target in brain injury in the premature infant

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