Increased inspired oxygen concentration as a factor in improved brain tissue oxygenation and tissue lactate levels after severe human head injury

Menzel, M.; Zauner, Alois; Soukup, Jens; Reinert, Michael; Bullock, Ross

doi:10.3171/jns.1999.91.1.0001

Cited by 271 publications

(65 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The current study performed in vitro using transient OGD taken together with the in vivo studies using transient global cerebral ischemia and reperfusion indicate that avoidance of hyperoxia during reoxgenation is an effective approach to reducing prelethal oxidative stress and subsequently improving brain cell survival. Caution should be taken in applying these results to other forms of brain injury, e.g., ischemic stroke and head trauma, as systemic hyperoxia may result in brain tissue normoxia and improved outcome under conditions that can exist in these disorders where tissue oxygenation can limit aerobic cerebral energy metabolism (Menzel et al, 1999;Singhal et al, 2005). Astrocyte oxygen/glucose deprivation (OGD) paradigm.…”

Section: Discussionmentioning

confidence: 99%

Hyperoxia promotes astrocyte cell death after oxygen and glucose deprivation

Danilov

Fiskum

2008

Glia

View full text Add to dashboard Cite

Astrocyte dysfunction and death accompany cerebral ischemia/reperfusion and possibly compromise neuronal survival. Animal studies indicate that neuronal death, neurologic injury, and oxidative molecular modifications are worse in animals exposed to hyperoxic compared to normoxic ventilation during reperfusion after global cerebral ischemia. It is unknown, however, whether ambient O 2 affects brain cell survival using in vitro ischemia paradigms where mechanisms of injury to specific cell types can be more thoroughly investigated. This study tested the hypothesis that compared with the supraphysiological level of 20% O 2 normally used in cell culture, lower, more physiological O 2 levels protect astrocytes from death following oxygen and glucose deprivation. Primary rat cortical astrocytes were cultured under either 7 or 20% O 2 , exposed to O 2 , and glucose deprivation for 4 h, and then exposed to normal medium under either 7 or 20% O 2 . Cell death and 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine immunoreactivities were assessed at different periods of reoxygenation. Astrocytes exposed to low levels of O 2 during reoxygenation undergo less death and exhibit lower levels of protein nitration and nucleic acid oxidation when compared with those under high levels of O 2 during reoxygenation. These results support the hypothesis that the 20% O 2 normally used in cell culture exacerbates astrocyte death and oxidative stress in an in vitro ischemia/reperfusion model compared to levels that more closely approximate those that exist in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

Hyperoxia promotes astrocyte cell death after oxygen and glucose deprivation

Danilov

Fiskum

2008

Glia

View full text Add to dashboard Cite

show abstract

“…Our present findings demonstrating reduced hippocampal protein tyrosine nitration and retention of PDHC enzyme activity with normoxic resuscitation support the need for additional preclinical and clinical studies to resolve this issue. The concept that hyperoxia worsens oxidative tissue damage and neurologic outcome after acute brain injury may not, however, apply to other forms of injury, e.g., stroke and trauma, as evidence suggests that hyperoxia can under some circumstances be beneficial [73][74][75][76][77]. The time during which the brain is exposed to high O 2 can also determine whether hyperoxia is helpful or detrimental.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Postischemic hyperoxia reduces hippocampal pyruvate dehydrogenase activity

Richards

Rosenthal

Kristián

et al. 2006

Free Radical Biology and Medicine

View full text Add to dashboard Cite

The pyruvate dehydrogenase complex (PDHC) is a mitochondrial matrix enzyme that catalyzes the oxidative decarboxylation of pyruvate and represents the sole bridge between anaerobic and aerobic cerebral energy metabolism. Previous studies demonstrating loss of PDHC enzyme activity and immunoreactivity during reperfusion after cerebral ischemia suggest that oxidative modifications are involved. This study tested the hypothesis that hyperoxic reperfusion exacerbates loss of PDHC enzyme activity, possibly due to tyrosine nitration or S-nitrosation. We used a clinically relevant canine ventricular fibrillation cardiac arrest model in which, after resuscitation and ventilation on either 100% O 2 (hyperoxic) or 21-30% O 2 (normoxic), animals were sacrificed at 2 h reperfusion and the brains removed for enzyme activity and immunoreactivity measurements. Animals resuscitated under hyperoxic conditions exhibited decreased PDHC activity and elevated 3-nitrotyrosine immunoreactivity in the hippocampus but not the cortex, compared to nonischemic controls. These measures were unchanged in normoxic animals. In vitro exposure of purified PDHC to peroxynitrite resulted in a dose-dependent loss of activity and increased nitrotyrosine immunoreactivity. These results support the hypothesis that oxidative stress contributes to loss of hippocampal PDHC activity during cerebral ischemia and reperfusion and suggest that PDHC is a target of peroxynitrite. KeywordsMitochondria; Hyperoxia; Nitrotyrosine; Normoxia; Oxidative stress; Global ischemia; Selective vulnerability; Free radicals Global cerebral ischemia and reperfusion cause severe neurochemical alterations, including oxidative modifications to lipids, proteins, and DNA. These and other covalent modifications can impair enzyme activities, including those necessary for energy metabolism. Alterations in these enzyme activities can limit postischemic aerobic metabolism and cellular ATP regeneration, thereby contributing to the pathophysiology of delayed neuronal cell death [1][2][3][4]. One enzyme known to be targeted and inactivated by reactive oxygen species is the pyruvate dehydrogenase complex (PDHC) [5]. Effects of ischemia/reperfusion on the PDHC can be particularly devastating because this enzyme forms the bridge between glycolysis and the Krebs cycle and can be the rate-limiting step in aerobic cerebral energy metabolism. NIH Public Access Author ManuscriptFree Radic Biol Med. Author manuscript; available in PMC 2008 October 21. Published in final edited form as:Free Radic Biol Med. 2006 June 1; 40(11): 1960-1970. doi:10.1016/j.freeradbiomed.2006.01.022. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe PDHC is located exclusively in the mitochondrial matrix and catalyzes the oxidative decarboxylation of pyruvate to form NADH and acetyl coenzyme A-the primary form of carbon that enters the Krebs cycle in the adult brain. Several laboratories have shown that PDHC enzyme activity is lost during cerebral ischemia/reperfusion [6][7][8]. PDHC im...

show abstract

“…Despite the total lack of knowledge regarding normal physiological values by these probes, focal "brain ischemia" has been reported in terms of "low oxygen" and "high lactate" 24 . In this respect, it is obvious that any brain tissue probe causes focal microvascular compression and distortion, which may well explain focal microcirculatory compressive hypoxia, with resulting increase in lactate concentration, findings that would be just artifactual, however.…”

Section: Diagnosing Brain Ischemia Diagnosing Brain Ischemia Diagnosimentioning

confidence: 99%

Expensive cerebral blood flow measurements alone are useless and misinformative in comatose patients: a comprehensive alternative

Cruz

2003

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

-Since the first report addressing quantification of cerebral blood flow (CBF), concomitant assessment of cerebral oxygen consumption was also carried out. Over the years, however, some investigators have emphatically and mistakenly addressed cerebral ischemia in comatose patients, on the basis of CBF measurements alone. In contrast, we have repeatedly reported that ischemia in these patients must be precisely evaluated based on CBF-metabolism coupling or uncoupling, rather than CBF alone. Based on these previous findings, we therefore propose a comprehensive alternative approach, namely the evaluation of brain ischemia in comatose patients based on cerebral metabolic parameters, such as cerebral extraction of oxygen or cerebral lactate release, without expensive CBF measurements.KEY WORDS: arteriojugular lactate difference, brain ischemia, cerebral blood flow, cerebral extraction of oxygen, coma.Medidas dispendiosas apenas de fluxo sanguíneo cerebral são inúteis e desinformativas em estados de Medidas dispendiosas apenas de fluxo sanguíneo cerebral são inúteis e desinformativas em estados de Medidas dispendiosas apenas de fluxo sanguíneo cerebral são inúteis e desinformativas em estados de Medidas dispendiosas apenas de fluxo sanguíneo cerebral são inúteis e desinformativas em estados de Medidas dispendiosas apenas de fluxo sanguíneo cerebral são inúteis e desinformativas em estados de coma: uma alternativa abrangente coma: uma alternativa abrangente coma: uma alternativa abrangente coma: uma alternativa abrangente coma: uma alternativa abrangente RESUMO -Desde o primeiro artigo apresentando quantificação de fluxo sanguíneo cerebral (FSC), também se avaliou o consumo cerebral de oxigênio. Todavia, ao longo dos anos, alguns investigadores têm enfaticamente e erroneamente destacado a isquemia cerebral em pacientes comatosos, baseando-se apenas em medidas do FSC. Em contrapartida, temos repetidamente destacado que a avaliação de isquemia cerebral nestes pacientes deve ser baseada no conceito de acoplamento ou desacoplamento entre metabolismo cerebral e FSC, ao invés de alterações no FSC apenas. Baseando-se nestes achados prévios, aqui propomos uma abordagem alternativa e abrangente, a qual envolve a avaliação de isquemia cerebral em pacientes comatosos baseando-se em parâmetros metabólicos cerebrais, tais como a extração cerebral de oxigênio ou a liberação cerebral de lactato, sem medidas dispendiosas de FSC. Since the pioneering work of Kety and Schmidt 1 , addressing quantification of cerebral blood flow (CBF), concomitant assessment of the cerebral metabolic rate of oxygen consumption (CMRO 2 ) was also established. CBF was precisely quantified as the integrated arteriojugular difference of nitrous oxide over approximately 10 minutes (the "height-overarea" method of quantification), whereas CMRO 2 was calculated as the product of CBF and the arteriojugular oxygen content difference (AVDO 2 ). The latter parameter had already been introduced in the pertinent literature by another pioneering work of Gibb...

show abstract

Increased inspired oxygen concentration as a factor in improved brain tissue oxygenation and tissue lactate levels after severe human head injury

Cited by 271 publications

References 69 publications

Hyperoxia promotes astrocyte cell death after oxygen and glucose deprivation

Hyperoxia promotes astrocyte cell death after oxygen and glucose deprivation

Postischemic hyperoxia reduces hippocampal pyruvate dehydrogenase activity

Expensive cerebral blood flow measurements alone are useless and misinformative in comatose patients: a comprehensive alternative

Contact Info

Product

Resources

About