van der Kaaij Niels P, Haitsma Jack J, Kluin Jolanda, Lambrecht Bart N, Lachmann Burkhard, de Bruin Ron W F, Bogers Ad J J C
Department of Cardio-Thoracic Surgery, Erasmus MC Rotterdam, Rotterdam, The Netherlands.
Eur J Cardiothorac Surg. 2005 May;27(5):774-82. doi: 10.1016/j.ejcts.2004.12.034.
To investigate whether surfactant pretreatment provides lung protection in an animal model of lung ischemia-reperfusion injury (LIRI).
Male Sprague-Dawley rats (n=100) were randomised to receive intratracheally administered surfactant or no pretreatment. One hour thereafter, animals underwent 120min of warm ischemia of the left lung, or were sham-operated. A third group served as healthy untreated controls. Animals were killed on day 1, 3 or 7. Blood gas values were measured and lung compliance was recorded. Broncho-alveolar lavage fluid (BALf) was obtained to assess the amount of alveolar protein, the ratio of small to large aggregate surfactant phospholipids (SA/LA ratio), and leukocyte infiltration (granulocytes, macrophages and lymphocytes, measured by Flow Cytometry).
LIRI resulted in a mortality rate of 17% and significantly decreased lung compliance and PaO(2) (day 1 and 3 P<0.001, day 7 P<0.05) as compared to sham-operated and healthy controls. On day 1 more protein was present in the alveoli of ischemic lungs (P<0.001) than in sham-operated and healthy controls. Furthermore, LIRI resulted in an increased SA/LA ratio in the left lung on day 1 (P<0.05) and caused infiltration of granulocytes (day 1, 3 and 7 (P<0.01)), macrophages (day 3 (P<0.05) and 7 (P<0.01) and lymphocytes (day 3 and 7 (P<0.01)) in the BALf as compared to sham-operated and healthy controls. Surfactant pretreatment improved survival, lung compliance (day 3 P<0.001) and PaO(2) (day 1, 3 (P<0.01 and 7 (P<0.05)). It also reduced protein leakage (P<0.05) and prevented an increase in the SA/LA ratio (P<0.01). Although the number of macrophages and granulocytes in the BALF was increased on day 1 and 3 (P<0.01) after surfactant pretreatment as compared to all other groups, the number of lymphocytes was reduced on day 3 (P<0.05).
The present study shows that surfactant pretreatment enhances recovery of lung function and lung mechanics after LIRI, resulting in normal parameters from day 3 onwards. Surfactant pretreatment in this LIRI model may provide useful information to improve donor lung function after lung transplantation.
研究表面活性剂预处理在肺缺血-再灌注损伤(LIRI)动物模型中是否提供肺保护作用。
将100只雄性Sprague-Dawley大鼠随机分为经气管内给予表面活性剂组或未进行预处理组。1小时后,对动物进行左肺120分钟的温缺血,或进行假手术。第三组作为未处理的健康对照组。在第1、3或7天处死动物。测量血气值并记录肺顺应性。获取支气管肺泡灌洗液(BALf)以评估肺泡蛋白量、小聚集与大聚集表面活性剂磷脂的比例(SA/LA比例)以及白细胞浸润情况(通过流式细胞术测量粒细胞、巨噬细胞和淋巴细胞)。
与假手术组和健康对照组相比,LIRI导致死亡率为17%,并显著降低肺顺应性和动脉血氧分压(第1天和第3天P<0.001,第7天P<0.05)。在第1天,缺血肺的肺泡中存在的蛋白比假手术组和健康对照组更多(P<0.001)。此外,LIRI导致第1天左肺的SA/LA比例增加(P<0.05),并导致BALf中粒细胞浸润(第1、3和7天(P<0.01))、巨噬细胞浸润(第3天(P<0.05)和第7天(P<0.01))以及淋巴细胞浸润(第3天和第7天(P<0.01)),与假手术组和健康对照组相比。表面活性剂预处理提高了生存率、肺顺应性(第3天P<0.001)和动脉血氧分压(第1天、第3天(P<0.01)和第7天(P<0.05))。它还减少了蛋白渗漏(P<0.05)并防止SA/LA比例增加(P<0.01)。尽管与所有其他组相比,表面活性剂预处理后第1天和第3天BALF中巨噬细胞和粒细胞数量增加(P<0.