Novick R J, Veldhuizen R A, Possmayer F, Lee J, Sandler D, Lewis J F
Division of Cardiovascular-Thoracic Surgery, University Hospital, London, Ontario, Canada.
J Thorac Cardiovasc Surg. 1994 Aug;108(2):259-68.
Previous work in our laboratory has documented alterations in surfactant composition and function after prolonged lung graft storage and transplantation in dogs (Am Rev Respir Dis 1993;148:208-15). To determine whether exogenous surfactant therapy was beneficial, we pretreated 13 canine double lung blocks with prostacyclin, flushed them with 4 degrees C modified Euro-Collins solution, and stored them at 4 degrees C for 37 to 38 hours. After left lung transplantation and immediately before reperfusion, eight dogs were administered 50 mg of bovine lung lipid extract surfactant per kilogram (50 mg/ml) directly into the left main bronchus and five served as nontreated control animals. Blood gases, peak inspired pressures, and individual pulmonary artery blood flows were measured every 30 minutes during 6 hours of reperfusion. The native right and transplanted left lungs were then lavaged and surfactant large and small aggregates and protein yields were analyzed. All nontreated animals had physiologic evidence of severe ischemia-reperfusion lung injury during reperfusion. Three of eight dogs treated with bovine lung lipid extract surfactant had near normal lung function at 6 hours of reperfusion, as reflected by maintenance of an oxygen tension/inspired oxygen fraction ratio of more than 400 mm Hg and a normal carbon dioxide tension. Five of eight dogs did not respond to surfactant therapy and had decreases in gas exchange identical to those of the control animals. Blood flow through the left pulmonary artery was maintained in the three animals that responded to exogenous surfactant, whereas flow significantly decreased to the left lung in all other animals, reflecting the patterns of gas exchange. In addition, the ratio of poorly functioning small surfactant aggregates to the well-functioning large aggregates isolated from lung lavage after 6 hours of reperfusion was decreased in surfactant-treated animals, especially in those exhibiting a beneficial physiologic response to surfactant therapy. We conclude that therapy with bovine lung lipid extract surfactant can result in excellent preservation of lung grafts after prolonged storage and transplantation, but that the results are not consistent. Further investigations are required to determine the factors responsible for the differential response to surfactant therapy.
我们实验室之前的研究记录了犬类肺移植长期保存和移植后表面活性剂成分及功能的改变(《美国呼吸与危重症医学杂志》1993年;148:208 - 15)。为了确定外源性表面活性剂治疗是否有益,我们用前列环素预处理了13个犬类双肺组织块,用4℃改良Euro - Collins溶液冲洗,然后在4℃下保存37至38小时。左肺移植后且在再灌注前,8只犬每千克体重经左主支气管直接给予50毫克牛肺脂质提取物表面活性剂(50毫克/毫升),5只作为未治疗的对照动物。在再灌注的6小时内,每30分钟测量一次血气、吸气峰压和各肺动脉血流量。然后对天然右肺和移植的左肺进行灌洗,并分析表面活性剂大小聚集体和蛋白质产量。所有未治疗的动物在再灌注期间都有严重缺血 - 再灌注肺损伤的生理证据。8只接受牛肺脂质提取物表面活性剂治疗的犬中,3只在再灌注6小时时肺功能接近正常,表现为氧分压/吸入氧分数比维持在400毫米汞柱以上且二氧化碳分压正常。8只犬中有5只对表面活性剂治疗无反应,气体交换下降程度与对照动物相同。对外源性表面活性剂有反应的3只动物左肺动脉血流得以维持,而所有其他动物左肺血流显著减少,这与气体交换模式相符。此外,在接受表面活性剂治疗的动物中,尤其是那些对表面活性剂治疗有有益生理反应的动物,再灌注6小时后从肺灌洗中分离出的功能不良的小表面活性剂聚集体与功能良好的大聚集体的比例降低。我们得出结论,牛肺脂质提取物表面活性剂治疗可在长期保存和移植后使肺移植得到良好保存,但结果并不一致。需要进一步研究以确定对表面活性剂治疗产生不同反应的相关因素。