Resuscitation of hypoxic piglets with 100% O2 increases pulmonary metalloproteinases and IL-8.
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.
Munkeby
Berit Holthe
BH
Department of Pediatric Research, Rikhospitalet University Hospital, Oslo, Norway. b.h.munkeby@medisin.uio.no
Børke
Wenche Bakken
WB
Bjørnland
Kristin
K
Sikkeland
Liv Ingunn B
LI
Borge
Grethe Iren A
GI
Lømo
Jon
J
Rivera
Santiago
S
Khrestchatisky
Michel
M
Halvorsen
Bente
B
Saugstad
Ola Didrik
OD
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
D017931:DNA Primers; D016209:Interleukin-8; D012333:RNA, Messenger; D045726:Metalloproteases