Beneficial effects of synthetic KL4-surfactant in experimental lung transplantation

Abstract

The aim of this study was to investigate whether intratracheal administration of a new synthetic surfactant that includes the cationic, hydrophobic 21-residue peptide KLLLLKLLLLKLLLLKLLLLK (KL4), might be effective in reducing ischemia-reperfusion injury after lung transplantation.

Single left lung transplantation was performed in Landrace pigs 22 hours post harvest. KL4-surfactant at a dose of 25 mg (2.5 mL)/kg total phospholipid was instilled at 37°C to the donor left lung (n=8) prior to explantation. Saline (2.5 mL·kg⁻¹; 37°C) was instilled into the donor left lung of the untreated group (n=6). Lung function in recipients was measured during 2 hr of reperfusion. Recipient left lung bronchoalveolar lavage (BAL) provided native cytometric, inflammatory marker, and surfactant data.

KL4-surfactant treatment recovered oxygen levels in the recipient blood (Pa,O2/FiO2 of 424±60 mm Hg vs. 263±101 mm Hg in untreated group; p=0.01) and normalized alveolar-arterial oxygen gradient. Surfactant biophysical function was also recovered in KL4-surfactant-treated lungs. This was associated with decreased C-reactive protein levels in BAL and recovery of surfactant protein A content, normalized protein/phospholipid ratios, and lower levels of both lipid peroxides and protein carbonyls in large surfactant aggregates.

These findings suggest an important protective role for KL4-surfactant treatment in lung transplantation.