Effects of Early Surfactant Treatment Persisting for One Week after Lung Transplantation in Rats

Abstract

We investigated whether pulmonary surfactant in rat lung transplants recovered during the first week post-transplantation, along with symptoms of the reimplantation response, and whether this recovery was affected by early surfactant treatment. The severity of pulmonary injury was varied by transplanting left lungs with 6-h and 20-h ischemia (n = 12 and 19, respectively). Half of the transplants were treated by instillation of surfactant before reperfusion. Lungs from sham operated, and normal rats (n = 4 and 5, respectively) served as controls. The pulmonary injury severely impaired lung transplant function; 10 of the worst affected animals died. After 1 wk, symptoms of reimplantation response and properties of pulmonary surfactant were assessed. If untreated, the reimplantation response had almost resolved in the 6-h but not in the 20-h ischemia group; pulmonary surfactant, however, continued to be deficient in both ischemia groups (low amounts of surfactant phospholipids and surfactant protein A [SP-A]). Surfactant treatment improved the recovery from injury in the 20-h ischemia group resulting in normal lung function and amounts of surfactant phospholipids. Amounts of SP-A were not improved by surfactant treatment. In conclusion, early surfactant treatment enhances recovery from transplantation injury and is persistently beneficial for pulmonary surfactant in lung transplants.

Surfactant pretreatment ameliorates ischemia-reperfusion injury of the lung

“…Since 1966, experimental data generated in lung transplantation models have provided evidence for surfactant abnormalities and depletion after lung ischemia-reperfusion injury (LIRI) [1][2][3][4][5][6]. In 1998, Hohlfeld and colleagues demonstrated surfactant alterations in human lung transplant recipients, more than 1 year after transplantation [7].…”

“…Because the endogenous surfactant pool is damaged by LIRI, the effect of surfactant replacement therapy has been investigated using experimental models of LIRI [1][2][3][4] addressed only the first few hours after reperfusion and focused mainly on treatment of the recipients. The administration of exogenous surfactant just before or after reperfusion resulted in improved lung function within hours after reperfusion [2,3].…”

Beneficial effects of synthetic KL4surfactant in experimental lung transplantation

“…Interestingly, these lung injury sequelae (i.e. high alveolar protein concentration and percentage of neutrophils in BAL) were absent 1 week after transplantation in animals treated with surfactant before reperfusion, but were not observed in untreated rats [9].…”

“…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].…”