title: Resuscitation with 100% O2 increases cerebral injury in hypoxemic piglets.
abstract: Perinatal asphyxia is a major cause of immediate and postponed brain injury in the newborn. We hypothesized that resuscitation with 100% O2 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% O2 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% O2 compared with 21% O2. Total MMP activity was doubled in resuscitated animals at endpoint compared with baseline (p=0.018), and the MMP-2 activity was significantly increased in piglets that were resuscitated with 21% O(2) (p=0.003) and 100% O2 (p=0.001) compared with baseline. MMP-2 mRNA level was 100% increased in piglets that were resuscitated with 100% O2 as compared with 21% O2 (p < 0.05). Oxygen radical absorbance capacity values in piglets that were resuscitated with 100% O2 were considerably reduced compared with both baseline (p=0.001) and piglets that were resuscitated with 21% O2 (p=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. Our findings suggest that resuscitation of asphyxiated piglets with 100% O2 is detrimental to the piglet brain compared with resuscitation with 21% O2.
authors.affiliation: Department of Pediatric Research, Rikshospitalet University Hospital, N-0027 Oslo, Norway. b.h.munkeby@klinmed.uio.no
authors.forename: Berit H
authors.initials: BH
authors.lastname: Munkeby
authors.forename: Wenche B
authors.initials: WB
authors.lastname: Børke
authors.forename: Kristin
authors.initials: K
authors.lastname: Bjørnland
authors.forename: Liv I B
authors.initials: LI
authors.lastname: Sikkeland
authors.forename: Grethe I A
authors.initials: GI
authors.lastname: Borge
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.forename: Ola D
authors.initials: OD
authors.lastname: Saugstad
mesh_terms: D000208:Acute Disease; D000388:Air; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism; D001927:Brain Diseases / Q000139:chemically induced* / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects; D005780:Gelatin; D005990:Glycerol / Q000378:metabolism; D000860:Hypoxia / Q000139:chemically induced* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D017551:Microdialysis; D010100:Oxygen / Q000097:blood / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D012151:Resuscitation / Q000009:adverse effects*; D034421:Sus scrofa
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D002245:Carbon Dioxide; D005780:Gelatin; D020778:Matrix Metalloproteinase 2; D005990:Glycerol; D010100:Oxygen