Becker P M, Pearse D B, Sylvester J T
Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
J Appl Physiol (1985). 1993 Sep;75(3):1233-7. doi: 10.1152/jappl.1993.75.3.1233.
In the ventilated ischemic lung, oxygen tension will increase at a time when glucose depletion may impair antioxidant defenses, thereby predisposing the lung to injury mediated by oxygen radicals. In the unventilated ischemic lung, however, glucose depletion in the setting of low oxygen tension may decrease production of ATP, leading to injury by a different mechanism. In this study, we evaluated the role of both oxygen tension and glucose concentration on ischemic injury in isolated ferret lungs. Injury, defined as an increase in vascular permeability, was assessed by measurement of filtration coefficient (Kf) and osmotic reflection coefficient for albumin (sigma alb) after 3 h of normothermic (37 degrees C) ischemia without reperfusion. Lungs were ventilated with either 95% O2-5% CO2 or 0% O2-5% CO2. The vasculature was flushed with physiological salt solution containing either 15 mM glucose (hyperoxia-glucose, anoxia-glucose), 15 mM sucrose (hyperoxia-sucrose, anoxia-sucrose), or no substrate (hyperoxia-no substrate, anoxia-no substrate) (n = 6 for each condition). Kf and sigma alb in hyperoxia-no substrate group did not differ from values in minimally ischemic normoxic normoglycemic ferret lungs. Without glucose, ischemic injury was worse in anoxic than in hyperoxic lungs. With glucose, ischemic injury was worse in hyperoxic than in anoxic lungs. Glucose exacerbated injury in hyperoxic, but not anoxic, lungs. These results indicate that ischemic injury in these lungs depended on both oxygen tension and glucose concentration and suggest that both oxygen radical generation and ATP depletion during ischemia may contribute to the development of this injury.
在通气的缺血肺中，当葡萄糖耗竭可能损害抗氧化防御机制时，氧分压会升高，从而使肺易于受到氧自由基介导的损伤。然而，在未通气的缺血肺中，低氧分压情况下的葡萄糖耗竭可能会减少ATP的生成，导致通过不同机制造成损伤。在本研究中，我们评估了氧分压和葡萄糖浓度对离体雪貂肺缺血性损伤的作用。损伤定义为血管通透性增加，在37℃常温缺血3小时且无再灌注后，通过测量滤过系数（Kf）和白蛋白的渗透反射系数（σalb）来评估。肺用95% O2 - 5% CO2或0% O2 - 5% CO2进行通气。血管用含有15 mM葡萄糖（高氧 - 葡萄糖、缺氧 - 葡萄糖）、15 mM蔗糖（高氧 - 蔗糖、缺氧 - 蔗糖）或无底物（高氧 - 无底物、缺氧 - 无底物）的生理盐溶液冲洗（每种情况n = 6）。高氧 - 无底物组的Kf和σalb与轻度缺血、常氧、血糖正常的雪貂肺的值无差异。没有葡萄糖时，缺氧肺的缺血性损伤比高氧肺更严重。有葡萄糖时，高氧肺的缺血性损伤比缺氧肺更严重。葡萄糖加重了高氧肺而非缺氧肺的损伤。这些结果表明，这些肺中的缺血性损伤取决于氧分压和葡萄糖浓度，并提示缺血期间氧自由基的产生和ATP的耗竭都可能促成这种损伤的发生。
