Kjaeve J, Naess L, Ingebrigtsen T, Vaage J, Bjertnaes L
Department of Anesthesiology, University of Tromsø, Norway.
Circ Shock. 1991 Apr;33(4):228-32.
Toxic oxygen metabolites (TOM) have been suggested to be mediators of permeability edema associated with the adult respiratory distress syndrome (ARDS). Because corticosteroids have possible beneficial effects in ARDS, we have examined the effect of methylprednisolone (MP) on TOM-induced lung edema in isolated, plasma-perfused rat lungs. TOM were generated by adding xanthine oxidase (XO) and hypoxanthine (HX) to the perfusate. Microvascular permeability was assessed by fluid filtration rate (FFR). FFR was determined before and 30 min after administration of XO and HX by measuring the weight increase of the lungs for the last 3 min during a standard 5 min elevation of the outlet pressure. MP was administered in two different ways: 1) Added to the perfusate 5 or 60 min before XO and HX (0.1 and 1 mg ml-1), and 2) given as pretreatment to the rats 12 and 2 hr before preparation of the lungs (40 mg kg -1). XO and HX significantly increased FFR compared to lungs perfused with untreated plasma. Pretreatment with MP significantly attenuated the increase in FFR caused by XO and HX. Addition of MP to the perfusate also inhibited the effect of TOM. This latter protection occurred irrespective of when MP was added before XO and HX. However, when the highest dose of MP was added 5 min before XO and HX, there was a loss of the protective effect. In summary, this study provides evidence that MP may directly prevent microvascular injury induced by TOM in isolated perfused rat lungs. The effect was dependent on the dose of MP applied, but not on when MP was administered prior to exposure to TOM.
毒性氧代谢产物（TOM）被认为是与成人呼吸窘迫综合征（ARDS）相关的渗透性肺水肿的介质。由于皮质类固醇在ARDS中可能具有有益作用，我们研究了甲基强的松龙（MP）对分离的、血浆灌注的大鼠肺中TOM诱导的肺水肿的影响。通过向灌注液中添加黄嘌呤氧化酶（XO）和次黄嘌呤（HX）来产生TOM。通过液体滤过率（FFR）评估微血管通透性。在给予XO和HX之前及之后30分钟，通过在标准的5分钟出口压力升高期间测量肺在最后3分钟的重量增加来确定FFR。MP以两种不同方式给药：1）在XO和HX之前5或60分钟添加到灌注液中（0.1和1 mg/ml），以及2）在制备肺之前12小时和2小时给予大鼠预处理（40 mg/kg）。与用未处理血浆灌注的肺相比，XO和HX显著增加了FFR。MP预处理显著减轻了XO和HX引起的FFR增加。向灌注液中添加MP也抑制了TOM的作用。无论MP在XO和HX之前何时添加，后一种保护作用都会发生。然而，当在XO和HX之前5分钟添加最高剂量的MP时，保护作用丧失。总之，本研究提供了证据表明MP可能直接预防分离的灌注大鼠肺中TOM诱导的微血管损伤。该作用取决于所用MP的剂量，但不取决于MP在暴露于TOM之前的给药时间。
