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.
The role of prostaglandin E1 (PgE1) and prostacyclin in enhancing the ischemic tolerance of single-lung grafts was investigated. Fifteen donor dogs underwent pulmonary artery flushing with 60 mL/kg of 4 °C modified Euro-Collins solution; 5 dogs each received a 15-minute infusion of PgE1, prostacyclin, or saline solution before flushing. After 12 hours of storage at 4 °C, left lung transplantation was performed in 15 recipient dogs. Measurements were performed after 10 minutes of right pulmonary artery snaring before transplantation, after transplantation, and after 2, 4, and 6 hours of reperfusion. At 6 hours, the oxygen tensions (on 100% O2) were 478 ± 64, 296 ± 75, 79 ± 12, and 71 ± 23 mm Hg in control (nontransplanted), prostacyclin-, PgE1-, and saline-treated dogs, respectively (p < 0.05, prostacyclin or control versus saline and PgE1 dogs). Mean pulmonary artery pressures increased within each group during reperfusion, but were not significantly different among groups. Similarly, peak inspiratory pressures and wet weight to dry weight ratios were not significantly different among groups after 6 hours of reperfusion. We conclude that donor pretreatment with prostacyclin is associated with superior oxygen transfer in canine lung allografts after 12 hours of cold storage, transplantation, and 6 hours of reperfusion. In this model, donor pretreatment with PgE1 conferred no benefit to prolonged lung allograft preservation.