Kiss Jan, Kääpä Pekka, Savunen Timo
Department of Surgery, Turku University Hospital, Turku, Finland.
Scand Cardiovasc J. 2007 Jun;41(3):186-91. doi: 10.1080/14017430601175459.
Acute lung injury and acute respiratory distress syndrome (ALI, ARDS) are well-known complications of cardiac and major vascular surgery. ARDS is associated with high mortality and no effective treatment is available. Protective effects of antioxidants or nitric oxide (NO) in experimental studies were not confirmed in clinical trials, but the potential beneficial effects of their combination are poorly known. This study was designed to investigate whether concomitant administration of NO donor and antioxidants has synergic effects on lung protection in ALI.
ALI was induced in rats by intestinal ischemia-reperfusion. Superoxide dismutase and catalase were administered as antioxidants and arginine as NO donor. Lung wet-dry ratio, MPO activity, tissue-air ratio, airspace hemorrhage and serum TNF-alpha were used as parameters of lung injury and systemic inflammation.
Antioxidants and arginine significantly reduced lung damage when administered separately. However, concomitant administration of antioxidants and arginine abolished the protective effects and enhanced systemic inflammation.
Our data suggests that antioxidants and NO in combination should be avoided in clinical practice.
急性肺损伤和急性呼吸窘迫综合征(ALI、ARDS)是心脏和大血管手术常见的并发症。ARDS死亡率高且尚无有效治疗方法。抗氧化剂或一氧化氮(NO)在实验研究中的保护作用在临床试验中未得到证实,但其联合使用的潜在益处知之甚少。本研究旨在探讨NO供体与抗氧化剂联合应用对ALI是否具有协同肺保护作用。
通过肠缺血再灌注诱导大鼠ALI。给予超氧化物歧化酶和过氧化氢酶作为抗氧化剂,给予精氨酸作为NO供体。肺湿干比、MPO活性、组织空气比、肺泡出血和血清TNF-α用作肺损伤和全身炎症的参数。
抗氧化剂和精氨酸单独给药时可显著减轻肺损伤。然而,抗氧化剂和精氨酸联合给药消除了保护作用并加重了全身炎症。
我们的数据表明,临床实践中应避免联合使用抗氧化剂和NO。