Novick R J, MacDonald J, Veldhuizen R A, Wan F, Duplan J, Denning L, Possmayer F, Gilpin A A, Yao L J, Bjarneson D, Lewis J F
Transplantation-Immunobiology Group, Robarts Research Institute, University Hospital, London, Ontario, Canada.
Am J Respir Crit Care Med. 1996 Jul;154(1):98-104. doi: 10.1164/ajrccm.154.1.8680706.
We have previously documented alterations in endogenous surfactant after lung transplantation and improved graft function in some dogs after instillation of bovine lipid extract surfactant (bLES) into the recipient. To determine the effect of bLES delivery method and timing of treatment on physiologic response and surfactant recovery, 21 canine left lung grafts were divided into four groups: (1) Treatment of the donor for 3 h with aerosolized bLES prior to graft storage (Donor Aerosol); (2) Treatment of the recipient with instilled bLES immediately after transplantation (Recipient Instilled); (3) No bLES treatment (Control); and (4) Aerosolized bLES in donors and instilled bLES in recipients (Combined Therapy). Aerosolized bLES was labeled with [3H]-dipalmitoylphosphatidylcholine (DPPC) and instilled bLES with [14C]-DPPC. Grafts were stored for 36 h, transplanted and reperfused for 6 h. The native right and transplanted left lungs were then lavaged and protein yield, surfactant aggregates, and bLES recovery were measured. After 6 h of reperfusion, PO2/FlO2 ratio was significantly better after Combined Therapy (372 +/- 52 mm Hg) than in the Recipient Instilled (117 +/- 47 mm Hg) and Control groups (87 +/- 26 mm Hg), with intermediate values in Donor Aerosol dogs (232 +/- 64 mm Hg). The recovery of donor aerosolized bLES from transplanted lungs was increased in dogs given Combined Therapy versus Donor Aerosol treatment alone (p = 0.03). Furthermore, with Combined Therapy there was an increased percentage of instilled bLES recovered from transplanted lungs compared with the Recipient Instilled group. We conclude that surfactant treatment strategies influence physiologic response and bLES recovery after prolonged lung preservation. Treatment of lung donors with exogenous surfactant prior to graft storage was associated with less severe lung injury. Combined donor and recipient bLES therapy resulted in a superior physiologic response during reperfusion in this model.
我们之前记录了肺移植后内源性表面活性剂的变化,并且在向受体滴注牛肺脂质提取物表面活性剂(bLES)后,部分犬的移植肺功能得到改善。为了确定bLES给药方法和治疗时机对生理反应及表面活性剂恢复的影响,将21个犬左肺移植分为四组:(1)在移植肺保存前,用雾化bLES对供体进行3小时治疗(供体雾化组);(2)移植后立即向受体滴注bLES(受体滴注组);(3)不进行bLES治疗(对照组);(4)供体雾化bLES且受体滴注bLES(联合治疗组)。雾化bLES用[3H] - 二棕榈酰磷脂酰胆碱(DPPC)标记,滴注bLES用[14C] - DPPC标记。移植肺保存36小时,移植并再灌注6小时。然后对天然右肺和移植的左肺进行灌洗,并测量蛋白质产量、表面活性剂聚集体和bLES回收率。再灌注6小时后,联合治疗组(372±52mmHg)的PO2/FlO2比值显著优于受体滴注组(117±47mmHg)和对照组(87±26mmHg),供体雾化组犬的该比值处于中间值(232±64mmHg)。与单独的供体雾化治疗相比,联合治疗组犬移植肺中供体雾化bLES的回收率增加(p = 0.03)。此外,与受体滴注组相比,联合治疗组从移植肺中回收的滴注bLES百分比增加。我们得出结论,表面活性剂治疗策略会影响长时间肺保存后的生理反应和bLES恢复。在移植肺保存前用外源性表面活性剂治疗供体与较轻的肺损伤相关。在该模型中,供体和受体联合bLES治疗在再灌注期间产生了更好的生理反应。