Increase in alveolar antioxidant levels in hyperoxic and anoxic ventilated rabbit lungs during ischemia.
Increases in free radicals are believed to play a central role in the development of pulmonary ischemia/reperfusion (I-R) injury, leading to microvascular leakage and deterioration of pulmonary surfactant. Continued ventilation during ischemia offers significant protection against I-R injury, but the impact of alveolar oxygen supply both on lung injury and on radical generation is still unclear. We investigated the influence of hyperoxic (95% O2) and anoxic (0% O2) ventilation during ischemia on alveolar antioxidant status and surfactant properties in isolated rabbit lungs. Normoxic and hyperoxic ventilated, buffer-perfused lungs (n = 5 or 6) and native lungs (n = 6) served as controls. As compared with controls, biophysical and biochemical surfactant properties were not altered in anoxic as well as hyperoxic ventilated ischemic (2, 3, and 4 h) lungs. Assessment of several antioxidants (reduced glutathione (GSH), alpha-tocopherol (vitamin E), retinol (vitamin A), ascorbic acid (vitamin C), uric acid, and plasmalogens (1-O-alkenyl-2-acyl-phospholipids)) in bronchoalveolar lavage fluid (BALF) revealed a significant increase in antioxidant compounds under anoxic and hyperoxic ventilation, with maximum levels occuring after 3 h of ischemia. For example, GSH increased to 5.1 +/- 0.8 microM (mean +/- SE, p <.001) after 3 h of anoxic ventilated ischemia and to 2.7 +/- 0.2 microM (p <.01) after hyperoxic ventilated ischemia compared with native controls (1.3 +/- 0.2 microM), but did not significantly change under anoxic and hyperoxic ventilation alone. In parallel, under ischemic conditions, oxidized glutathione (GSSG) increased during hyperoxic (3 h: 0.81 +/- 0.04 microM, p <.001), but remained unchanged during anoxic (3 h: 0.31 +/- 0.04 microM) ventilation compared with native controls (0.22 +/- 0.02 microM), whereas F2-isoprostanes were elevated under both hyperoxic (3 h: 63 +/- 15 pM, p <.01) and anoxic (3 h: 50 +/- 9 pM, p <.01) ventilation compared with native controls (16 +/- 4 pM). We conclude that oxidative stress is increased in the lung alveolar lining layer during ischemia, during both anoxic and hyperoxic ventilation. This is paralleled by an increase rather than a decrease in alveolar antioxidant levels, suggested to reflect an adaptive response to oxidative stress during ischemia.
Schmidt
Reinhold
R
Medizinische Klinik II, Zentrum für Innere Medizin, Justus-Liebig-University, Giessen, Germany. reinhold.schmidt@innere.med.uni-giessen.de
Schäfer
Christoph
C
Luboeinski
Thomas
T
Löckinger
Alexander
A
Hermle
Gerd
G
Grimminger
Friedrich
F
Seeger
Werner
W
Ghofrani
Ardeschir
A
Schütte
Hartwig
H
Günther
Andreas
A
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018496:Hyperoxia / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D010084:Oxidation-Reduction; D010955:Plasmalogens / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism; D012123:Pulmonary Ventilation; D011817:Rabbits; D014527:Uric Acid / Q000378:metabolism; D014815:Vitamins / Q000378:metabolism
D000975:Antioxidants; D010955:Plasmalogens; D011663:Pulmonary Surfactants; D014815:Vitamins; D014527:Uric Acid; D007770:L-Lactate Dehydrogenase