Beneficial effects of synthetic KL₄ surfactant in experimental lung transplantation.
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 ischaemia-reperfusion injury after lung transplantation. Single left lung transplantation was performed in Landrace pigs 22 h post-harvest. KL₄ surfactant at a dose of 25 mg total phospholipid·kg body weight⁻¹ (2.5 mL·kg body weight⁻¹) was instilled at 37°C to the donor left lung (n = 8) prior to explantation. Saline (2.5 mL·kg body weight⁻¹; 37°C) was instilled into the donor left lung of the untreated group (n = 6). Lung function in recipients was measured during 2 h of reperfusion. Recipient left lung bronchoalveolar lavage (BAL) provided native cytometric, inflammatory marker and surfactant data. KL(4) surfactant treatment recovered oxygen levels in the recipient blood (mean ± sd arterial oxygen tension/inspiratory oxygen fraction 424 ± 60 versus 263 ± 101 mmHg in untreated group; p=0.01) and normalised alveolar-arterial oxygen tension difference. 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, normalised 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.
Sáenz
A
A
Dept of Biochemistry and Molecular Biology I, Complutense University and CIBERES (Respiratory Research Center), Madrid, Spain.
Alvarez
L
L
Santos
M
M
López-Sánchez
A
A
Castillo-Olivares
J L
JL
Varela
A
A
Segal
R
R
Casals
C
C
D000327:Adsorption; D000818:Animals; D018893:Bronchoalveolar Lavage; D002097:C-Reactive Protein / Q000378:metabolism; D002244:Carbon / Q000737:chemistry; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins; D015227:Lipid Peroxidation; D008168:Lung / Q000187:drug effects; D016040:Lung Transplantation / Q000379:methods*; D010100:Oxygen / Q000737:chemistry; D010455:Peptides / Q000494:pharmacology*; D010743:Phospholipids / Q000737:chemistry; D011663:Pulmonary Surfactants / Q000737:chemistry; D015427:Reperfusion Injury; D013499:Surface Properties; D013552:Swine
D036341:Intercellular Signaling Peptides and Proteins; C097558:KL4 surfactant; D010455:Peptides; D010743:Phospholipids; D011663:Pulmonary Surfactants; D002244:Carbon; D002097:C-Reactive Protein; D010100:Oxygen