Hyperbaric oxygen toxicity: role of thromboxane.
Exposing rabbits for 1 h to 100% O2 at 4 atm barometric pressure markedly increases the concentration of thromboxane B2 in alveolar lavage fluid [1,809 +/- 92 vs. 99 +/- 24 (SE) pg/ml, P less than 0.001], pulmonary arterial pressure (110 +/- 17 vs. 10 +/- 1 mmHg, P less than 0.001), lung weight gain (14.6 +/- 3.7 vs. 0.6 +/- 0.4 g/20 min, P less than 0.01), and transfer rates for aerosolized 99mTc-labeled diethylenetriamine pentaacetate (500 mol wt; 40 +/- 14 vs. 3 +/- 1 x 10(-3)/min, P less than 0.01) and fluorescein isothiocyanate-labeled dextran (7,000 mol wt; 10 +/- 3 vs. 1 +/- 1 x 10(-4)/min, P less than 0.01). Pretreatment with the antioxidant butylated hydroxyanisole (BHA) entirely prevents the pulmonary hypertension and lung injury. In addition, BHA blocks the increase in alveolar thromboxane B2 caused by hyperbaric O2 (10 and 45 pg/ml lavage fluid, n = 2). Combined therapy with polyethylene glycol- (PEG) conjugated superoxide dismutase (SOD) and PEG-catalase also completely eliminates the pulmonary hypertension, pulmonary edema, and increase in transfer rate for the aerosolized compounds. In contrast, combined treatment with unconjugated SOD and catalase does not reduce the pulmonary damage. Because of the striking increase in pulmonary arterial pressure to greater than 100 mmHg, we tested the hypothesis that thromboxane causes the hypertension and thus contributes to the lung injury. Indomethacin and UK 37,248-01 (4-[2-(1H-imidazol-1-yl)-ethoxy]benzoic acid hydrochloride, an inhibitor of thromboxane synthase, completely eliminate the pulmonary hypertension and edema.(ABSTRACT TRUNCATED AT 250 WORDS)
Jacobson
J M
JM
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Michael
J R
JR
Meyers
R A
RA
Bradley
M B
MB
Sciuto
A M
AM
Gurtner
G H
GH
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D006931:Hyperbaric Oxygenation / Q000009:adverse effects*; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D055370:Lung Injury; D008297:Male; D011654:Pulmonary Edema / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology; D013929:Thromboxane B2 / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D007093:Imidazoles; C029166:dazoxiben; D002083:Butylated Hydroxyanisole; D013929:Thromboxane B2; D013482:Superoxide Dismutase; D013930:Thromboxane-A Synthase; D007213:Indomethacin