Resuscitation with 100% oxygen causes intestinal glutathione oxidation and reoxygenation injury in asphyxiated newborn piglets.
OBJECTIVE
To compare mesenteric blood flow, oxidative stress, and mucosal injury in piglet small intestine during hypoxemia and reoxygenation with 21%, 50%, or 100% oxygen.


BACKGROUND
Necrotizing enterocolitis is a disease whose pathogenesis likely involves hypoxia-reoxygenation and the generation of oxygen-free radicals, which are known to cause intestinal injury. Resuscitation of asphyxiated newborns with 100% oxygen has been shown to increase oxidative stress, as measured by the glutathione redox ratio, and thus may predispose to free radical-mediated tissue injury.


METHODS
Newborn piglets subjected to severe hypoxemia for 2 hours were resuscitated with 21%, 50%, or 100% oxygen while superior mesenteric artery (SMA) flow and hemodynamic parameters were continuously measured. Small intestinal tissue samples were analyzed for histologic injury and levels of oxidized and reduced glutathione.


RESULTS
SMA blood flow decreased to 34% and mesenteric oxygen delivery decreased to 9% in hypoxemic piglets compared with sham-operated controls. With reoxygenation, SMA blood flow increased to 177%, 157%, and 145% of baseline values in piglets resuscitated with 21%, 50%, and 100% oxygen, respectively. Mesenteric oxygen delivery increased to more than 150% of baseline values in piglets resuscitated with 50% or 100% oxygen, and this correlated significantly with the degree of oxidative stress, as measured by the oxidized-to-reduced glutathione ratio. Two of eight piglets resuscitated with 100% oxygen developed gross and microscopic evidence of pneumatosis intestinalis and severe mucosal injury, while all other piglets were grossly normal.


CONCLUSIONS
Resuscitation of hypoxemic newborn piglets with 100% oxygen is associated with an increase in oxygen delivery and oxidative stress, and may be associated with the development of small intestinal hypoxia-reoxygenation injury. Resuscitation of asphyxiated newborns with lower oxygen concentrations may help to decrease the risk of necrotizing enterocolitis.
Department of Surgery, University of Alberta Hospital, University of Alberta, Edmonton, Alberta, Canada.
Erika
E
Haase
David L
DL
Bigam
Quentin B
QB
Nakonechny
Laurence D
LD
Jewell
Gregory
G
Korbutt
Po-Yin
PY
Cheung
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000175:diagnosis / Q000628:therapy*; D001707:Biopsy, Needle; D001784:Blood Gas Analysis; D020345:Enterocolitis, Necrotizing / Q000209:etiology / Q000473:pathology*; D005260:Female; D019803:Glutathione Disulfide / Q000032:analysis / Q000378:metabolism*; D006439:Hemodynamics / Q000502:physiology; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D010100:Oxygen / Q000009:adverse effects* / Q000627:therapeutic use; D011336:Probability; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology; D012151:Resuscitation / Q000009:adverse effects* / Q000379:methods; D013152:Splanchnic Circulation / Q000502:physiology; D013552:Swine
D010100:Oxygen; D019803:Glutathione Disulfide