Jacobson J M, Michael J R, Meyers R A, Bradley M B, Sciuto A M, Gurtner G H
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Appl Physiol (1985). 1992 Feb;72(2):416-22. doi: 10.1152/jappl.1992.72.2.416.
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)
将兔子在4个大气压的气压下暴露于100%氧气中1小时，可显著增加肺泡灌洗液中血栓素B2的浓度[1,809±92 vs. 99±24（SE）pg/ml，P<0.001]、肺动脉压（110±17 vs. 10±1 mmHg，P<0.001）、肺重量增加（14.6±3.7 vs. 0.6±0.4 g/20分钟，P<0.01），以及雾化的99mTc标记的二乙三胺五乙酸（分子量500；40±14 vs. 3±1×10⁻³/min，P<0.01）和异硫氰酸荧光素标记的葡聚糖（分子量7,000；10±3 vs. 1±1×10⁻⁴/min，P<0.01）的转运速率。用抗氧化剂叔丁基对羟基茴香醚（BHA）预处理可完全预防肺动脉高压和肺损伤。此外，BHA可阻止高压氧引起的肺泡血栓素B2增加（灌洗液中10和45 pg/ml，n = 2）。聚乙二醇（PEG）偶联的超氧化物歧化酶（SOD）和PEG - 过氧化氢酶联合治疗也完全消除了肺动脉高压、肺水肿以及雾化化合物转运速率的增加。相比之下，未偶联的SOD和过氧化氢酶联合治疗并不能减轻肺损伤。由于肺动脉压显著升高至大于100 mmHg，我们检验了血栓素导致高血压并因此促成肺损伤的假说。吲哚美辛和UK 37,248 - 01（4 - [2 - （1H - 咪唑 - 1 - 基） - 乙氧基]苯甲酸盐酸盐，一种血栓素合酶抑制剂）可完全消除肺动脉高压和水肿。（摘要截短于250字）
