Beneficial effects of synthetic KL4 surfactant in experimental lung transplantation

被引:12
作者
Saenz, A. [1 ,2 ]
Alvarez, L. [3 ]
Santos, M. [3 ]
Lopez-Sanchez, A. [1 ,2 ]
Castillo-Olivares, J. L. [3 ]
Varela, A. [4 ]
Segal, R. [5 ]
Casals, C. [1 ,2 ]
机构
[1] Univ Complutense, Dept Biochem & Mol Biol 1, E-28040 Madrid, Spain
[2] CIBERES Resp Res Ctr, Madrid, Spain
[3] Puerta de Hierro Univ Hosp, Dept Expt Surg, Madrid, Spain
[4] Puerta de Hierro Univ Hosp, Dept Thorac Surg, Madrid, Spain
[5] Discovery Labs Inc, Warrington, PA USA
关键词
C-reactive protein; inflammation; ischaemia-reperfusion injury; lipid peroxidation; lung surfactant; protein carbonyls; C-REACTIVE PROTEIN; RESPIRATORY-DISTRESS-SYNDROME; PRIMARY GRAFT DYSFUNCTION; PULMONARY SURFACTANT; REPERFUSION INJURY; SP-B; LUCINACTANT; EXPRESSION; ISCHEMIA; TRIAL;
D O I
10.1183/09031936.00020810
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
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 degrees C to the donor left lung (n=8) prior to explantation. Saline (2.5 mL.kg body weight(-1); 37 degrees 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. KL4 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.
引用
收藏
页码:925 / 932
页数:8
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