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

The finding that human AMFs are maintained in the lung parenchyma for several years indicates that pulmonary macrophage transplantation can be a feasible therapeutic option for patients with diseases caused by dysfunctional AMFs. Moreover, in a lung transplantation setting, long-term persistence of donor AMFs may be important for the development of chronic graft rejection.

We hypothesized that resuscitation with 100% O 2 compared with 21% O 2 is detrimental to pulmonary tissue. The pulmonary injury was assessed by matrix metalloproteinase (MMP) activity, oxidative stress, IL-8, and histology 2.5 h after resuscitation from a hypoxic state. In pulmonary tissue extracts, MMP activity was analyzed by broad matrix-degrading capacity (total MMP) and zymography. MMP-2 mRNA expression was evaluated by quantitative real-time PCR. Total endogenous antioxidant capacity was measured by the oxygen radical absorbance capacity (ORAC) assay, and IL-8 was analyzed by ELISA technique. In bronchoalveolar lavage (BAL) fluid, MMPs were analyzed by zymography. In pulmonary tissue, pro-and active MMP-2 levels were increased in piglets that were resuscitated with 100% O 2 compared with 21% O 2 . Pro-MMP-9, total MMP activity, and MMP-2 mRNA levels were significantly increased in resuscitated piglets compared with baseline. Net gelatinolytic activity increased in submucosa and blood vessels after 100% O 2 and only in the blood vessels after 21% O 2 . Compared with baseline, ORAC values were considerably lowered in the resuscitated piglets and significantly reduced in the 100% O 2 versus 21% O 2 group. In BAL fluid, both pro-MMP-9 and pro-MMP-2 increased 2-fold in the 100% O 2 group compared with 21% O 2 . Moreover, IL-8 concentration increased significantly in piglets that were resuscitated with 100% O 2 compared with 21% O 2 , suggesting a marked proinflammatory response in the pulmonary tissue. Altogether, these data strongly suggest that caution must be taken when applying pure O 2 to the newborn infant. Traditionally, asphyxiated newborn infants have been resuscitated with 100% O 2 . This recommendation is based mainly on precedent rather than sound evidence. Hyperoxia leads to generation of O 2 free radicals, which have a role in reperfusion injury after asphyxia (1). Naturally, the lung is exposed directly to the highest partial pressure of inspired O 2 , and pulmonary damage, as a result of O 2 exposure, is a serious clinical complication in infants who require high levels of O 2 as treatment (2). It is important not only to provide adequate O 2 consumption in organs but also to prevent further tissue damage during resuscitation caused by reoxygenation injury or O 2 toxicity. This might be achieved by lowering the O 2 concentration during resuscitation. There is therefore an ongoing debate whether to use 21% or 100% O 2 in neonatal resuscitation (3).Matrix metalloproteinases (MMPs) are involved in the pathogenesis of tissue inflammation and wound healing in lung injury (4,5). The role of oxidative stress and its toxic effects on lipids, as well as on disruption of extracellular matrix through up-regulation of MMPs, is well established (6,7). Reduced Received November 19, 2004; accepted February 1, 2005

Compared to unexposed controls, the hairdressers had signs of neutrophilic airway inflammation, higher eNO levels and higher CRP. The hairdressers were exposed to high concentrations of ammonia from hairdressing chemicals and their working conditions were unsatisfactory.