Postoperative hyperoxia (60%) worsens hepatic injury in mice.

Anesthesiology (2014-09-17)
Quirin Zangl, André Martignoni, Sharon H Jackson, Akio Ohta, Brenda Klaunberg, Ines Kaufmann, Dimitry Lukashev, Jerrold M Ward, Michail Sitkovsky, Manfred Thiel, Alexander Choukèr
ABSTRACT

Liver damage by ischemia and reperfusion injury is a risk factor for morbidity and mortality after liver surgery. Postoperative oxygen treatment is routinely applied in the postanesthesia and intensive care unit after liver surgery. The risks of aggravating the injury by increasing inspiratory oxygen from 21 to 60% in the postoperative period were investigated in mice. Parameters of liver injury were compared after induction of hepatic ischemia-reperfusion injury, by clamping the left liver lobe for 45 min, and reperfusion for 24 h either under normoxic (21% oxygen) or hyperoxic (60% oxygen) conditions (n=22 per group). The extent of tissue injury and oxidative responses was analyzed in the presence or absence of polymorphonuclear leukocytes, functional Kupffer cells, and the p47phox unit of the nicotinamide adenine dinucleotide phosphate oxidase (n=6 to 11 per group). Compared with postoperative normoxic conditions, hyperoxia increased cell damage (glutamate-pyruvate transaminase: 1,870 [±968 SD] vs. 60% 2,981 [±1,038 SD], 21 vs. 60% oxygen, in U/l as mean±SD; P<0.01), liver weights (341±52 vs. 383±44, 21 vs. 60% oxygen, in mg as mean±SD; P=0.02), damage scores (1.9±0.8 vs. 3.1±1.0, 21 vs. 60% oxygen, score as mean±SD; P=0.02), and reactive oxygen species (15.0±12.0 vs. 30.4±19.2, 21 vs. 60% oxygen, in μmol/l as mean±SD; P<0.05). The aggravation of the tissue damaging effects as a result of hyperoxia was not seen in mice with depletions of polymorphonuclear leukocytes or Kupffer cells, or with nonfunctioning nicotinamide adenine dinucleotide phosphate oxidase. Liver injury after ischemia was significantly aggravated by hyperoxia as a consequence of immune cell-mediated oxidative burst. Further studies are needed to elucidate whether routine delivery of high inspirational oxygen concentrations postoperatively should be limited.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
2-(4-Hydroxyphenylazo)benzoic acid, ≥95% (HPLC)
Sigma-Aldrich
Gadolinium(III) chloride, anhydrous, powder, 99.99% trace metals basis
Supelco
2-(4-Hydroxyphenylazo)benzoic acid, matrix substance for MALDI-MS, ≥99.5%
Supelco
Gadolinium(III) chloride solution, NMR reference standard, water 1 %, DSS 0.1 %, 0.1 mg/mL in D2O (99.9 atom % D), NMR tube size 5 mm × 8 in.
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Supelco
Gadolinium(III) chloride solution, NMR reference standard, 0.1 mg/mL in D2O (99.9 atom % D), Methanol-13C 0.1 % (99 atom % 13C), water 1 %, NMR tube size 5 mm × 8 in.
Sigma-Aldrich
Gadolinium(III) chloride solution, NMR reference standard, 0.1 mg/mL in D2O (99.9 atom % D), water 0.1 %, NMR tube size 6.5 mm × 8 in.
Supelco
Gadolinium(III) chloride solution, NMR reference standard, 0.1 mg/mL in D2O (99.9 atom % D), water 1 %, DSS 0.1 %, NMR tube size 8 mm × 8 in.
Supelco
Gadolinium(III) chloride solution, NMR reference standard, 0.1 mg/mL in D2O (99.9 atom % D), DSS 0.1 %, water 1 %, NMR tube size 3 mm × 8 in.