title: Resuscitation of hypoxic piglets with 100% O2 increases pulmonary metalloproteinases and IL-8.
abstract: We hypothesized that resuscitation with 100% O2 compared with 21% O2 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% O2 compared with 21% O2. 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% O2 and only in the blood vessels after 21% O2. Compared with baseline, ORAC values were considerably lowered in the resuscitated piglets and significantly reduced in the 100% O2 versus 21% O2 group. In BAL fluid, both pro-MMP-9 and pro-MMP-2 increased 2-fold in the 100% O2 group compared with 21% O2. Moreover, IL-8 concentration increased significantly in piglets that were resuscitated with 100% O2 compared with 21% O2, suggesting a marked proinflammatory response in the pulmonary tissue. Altogether, these data strongly suggest that caution must be taken when applying pure O2 to the newborn infant.
authors.affiliation: Department of Pediatric Research, Rikhospitalet University Hospital, Oslo, Norway. b.h.munkeby@medisin.uio.no
authors.forename: Berit Holthe
authors.initials: BH
authors.lastname: Munkeby
authors.forename: Wenche Bakken
authors.initials: WB
authors.lastname: Børke
authors.forename: Kristin
authors.initials: K
authors.lastname: Bjørnland
authors.forename: Liv Ingunn B
authors.initials: LI
authors.lastname: Sikkeland
authors.forename: Grethe Iren A
authors.initials: GI
authors.lastname: Borge
authors.forename: Jon
authors.initials: J
authors.lastname: Lømo
authors.forename: Santiago
authors.initials: S
authors.lastname: Rivera
authors.forename: Michel
authors.initials: M
authors.lastname: Khrestchatisky
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.forename: Ola Didrik
authors.initials: OD
authors.lastname: Saugstad
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D000860:Hypoxia / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000201:enzymology* / Q000378:metabolism*; D045726:Metalloproteases / Q000096:biosynthesis* / Q000235:genetics; D010102:Oxygen Inhalation Therapy; D012333:RNA, Messenger / Q000235:genetics; D013552:Swine
chemical_list: D017931:DNA Primers; D016209:Interleukin-8; D012333:RNA, Messenger; D045726:Metalloproteases