Evaluation of surfactant treatment strategies after prolonged graft storage in lung transplantation.

Abstract

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.

Pre-ischaemic exogenous surfactant reduces pulmonary injury in rat ischaemia/reperfusion

“…Several experimental [12][13][14][15][16][17][18][19][20][21] and clinical [22][23][24] studies give evidence that exogenous surfactant therapy successfully supplements the imbalanced endogenous surfactant system, serving to attenuate I/R injury and effectively improve lung preservation and graft function [11]. The great advantage of exogenous surfactant therapy of the donor in human lung transplantation is the fact that PGD in this case can accurately be predicted and, thus, even be prevented, providing a promising approach for prophylactic surfactant therapy [11,25,26].…”

Donor pretreatment with ambroxol or dexamethasone fails to ameliorate reperfusion injury in experimental lung transplantation

“…In order to prevent deterioration of graft function following clinical lung transplantation, supplementation of the donor graft with exogenous surfactant has been proposed [26]. Studies by Novick et al [25] and Hausen et al [ 171 have emphasized the importance of early donor treatment as the preferred treatment modality, with surfactant given in a dose of 100-200mg/ kg. At the present unit cost of exogenous surfactant, however, this type of treatment strategy may not be financially feasible for clinical use.…”

“…Experimental studies by Novick et al [25] and Hausen et al [17] have shown that replacement therapy with as little as 20-100 mg/kg of exogenous bovine surfactant can result in dramatic improvement in early postoperative graft function. However, the current high costs of surfactant may limit the practicality of this therapeutic option.…”

Beneficial effects of synthetic KL4surfactant in experimental lung transplantation

“…The therapeutic dose we used for intratracheal administration of KL 4 surfactant (25 mg?kg body weight -1 ) to donor lungs is ,15% of the dose recommended for surfactant instillation in neonatal RDS (175 mg/kg bw), and much lower than that used for the treatment of patients with ARDS (100-300 mg?kg body weight -1 ) [19] and that previously used in experimental lung transplantation (50-200 mg?kg body weight -1 ) [8][9][10][11][12][13]. We found that a higher dose of KL 4 surfactant (65 mg?kg body weight -1 (2.5 mL?kg body weight -1 ) did not increase the beneficial effect of this synthetic surfactant (data not shown).…”

“…In various experimental [8][9][10][11][12][13] and clinical [14][15][16][17][18] lung transplantation studies, animal-derived surfactants have been administered at different times over the course of the injury, either to the donor (before ischaemia) [8,10,12,13,16] or to the recipient (before [9][10][11]17] or after [12][13][14][15]18] reperfusion). Animal-derived surfactants consist of lipid extract preparations obtained from either bovine or porcine sources [19].…”