Mehaffey J Hunter, Charles Eric J, Sharma Ashish K, Salmon Morgan, Money Dustin, Schubert Sarah, Stoler Mark H, Tribble Curtis G, Laubach Victor E, Roeser Mark E, Kron Irving L
Department of Surgery, University of Virginia, Charlottesville, Virginia.
Department of Pathology, University of Virginia, Charlottesville, Virginia.
Ann Thorac Surg. 2017 Jun;103(6):1723-1729. doi: 10.1016/j.athoracsur.2017.01.018. Epub 2017 Apr 21.
Sepsis is the number one cause of lung injury in adults. Ex vivo lung perfusion (EVLP) is gaining clinical acceptance for donor lung evaluation and rehabilitation and may expand the use of marginal organs for transplantation. We hypothesized that 4 hours of normothermic EVLP would improve compliance and oxygenation in a porcine model of sepsis-induced lung injury.
We used intravenous lipopolysaccharide (LPS) to induce a systemic inflammatory response in a porcine model of lung injury. Two groups of 4 animals each received a 2-hour infusion of LPS through the external jugular vein. Serial measurements of blood gases were performed every 30 minutes until the partial pressure of oxygen/fraction of inspired oxygen ratio dropped below 150 on two consecutive readings. Lungs were then randomized to treatment with 4 hours of normothermic EVLP with STEEN Solution (XVIVO Perfusion Inc, Englewood, CO) or 4 additional hours of in vivo perfusion (control). Airway pressures and blood gases were recorded for calculation of dynamic lung compliance and partial pressure of oxygen/fraction of inspired oxygen ratios. EVLP was performed with hourly recruitment maneuvers and oxygen challenge.
All animals reached a partial pressure of oxygen/fraction of inspired oxygen ratio of less than 150 mm Hg within 3 hours after start of the LPS infusion. Oxygenation and compliance in the control animals continued to decline during the 4-hour in vivo perfusion period, and 3 of the 4 animals died of severe hypoxia within 4 hours. The EVLP group demonstrated significant improvements hour 1 to hour 4 in oxygenation (365.8 ± 53.0 vs 584.4 ± 21.0 mm Hg, p = 0.02) and dynamic compliance (9.0 ± 2.8 vs 15.0 ± 3.6, p = 0.02 mL/cm HO).
EVLP successfully rehabilitated LPS-induced lung injury in this preclinical porcine model and may thus provide a means to rehabilitate many types of acute lung injury.
脓毒症是成人肺损伤的首要原因。体外肺灌注（EVLP）在供体肺评估和修复方面正逐渐获得临床认可，并且可能扩大边缘器官在移植中的应用。我们假设在脓毒症诱导的肺损伤猪模型中，4小时的常温EVLP可改善肺顺应性和氧合。
我们使用静脉注射脂多糖（LPS）在猪肺损伤模型中诱导全身炎症反应。两组，每组4只动物，通过颈外静脉接受2小时的LPS输注。每30分钟进行一次血气的连续测量，直至氧分压/吸入氧分数比在连续两次读数时降至150以下。然后将肺随机分为两组，分别用STEEN溶液（XVIVO灌注公司，科罗拉多州恩格尔伍德）进行4小时的常温EVLP治疗或再进行4小时的体内灌注（对照组）。记录气道压力和血气以计算动态肺顺应性和氧分压/吸入氧分数比。EVLP过程中每小时进行一次肺复张手法和氧激发试验。
所有动物在LPS输注开始后3小时内氧分压 / 吸入氧分数比均低于150 mmHg。在4小时的体内灌注期间，对照组动物的氧合和顺应性持续下降，4只动物中有3只在4小时内死于严重缺氧。EVLP组在第1小时至第4小时氧合（365.8 ± 53.0 vs 584.4 ± 21.0 mmHg，p = 0.02）和动态顺应性（9.0 ± 2.8 vs 15.0 ± 3.6，p = 0.02 mL/cm H₂O）方面有显著改善。
在这个临床前猪模型中，EVLP成功修复了LPS诱导的肺损伤，因此可能为修复多种类型的急性肺损伤提供一种方法。
