Beneficial effects of synthetic KL₄surfactant 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 (KL 4 ), might be effective in reducing ischaemia-reperfusion injury after lung transplantation.Single left lung transplantation was performed in Landrace pigs 22 h post-harvest. KL 4 surfactant at a dose of 25 mg total phospholipid?kg body weight -1 (2.5 mL?kg body weight -1) was instilled at 37uC to the donor left lung (n58) prior to explantation. Saline (2.5 mL?kg body weight -1 ; 37uC) was instilled into the donor left lung of the untreated group (n56). 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; p50.01) and normalised alveolar-arterial oxygen tension difference. Surfactant biophysical function was also recovered in KL 4 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 KL 4 surfactant treatment in lung transplantation.

A standardized model of brain death, donor treatment, and lung transplantation for studies on organ preservation and reconditioning

“…After brain death induction and donor treatment, the lungs were retrieved and cold-stored for 8 h. This time interval represents a realistic frame for potential lung preservation and/or reconditioning strategies. Similar to other investigations, we have then used a single lung transplantation procedure [ 39 , 40 ]. Lung function early after reperfusion has been carefully monitored, as reperfusion injury is generally considered an outcome measure in lung preservation studies [ 41 ].…”

Oxidative and nitrosative stress during pulmonary ischemia-reperfusion injury: from the lab to the OR

“…Surfactant can be administered before ischemia (85), and before (86) or during (87) reperfusion. Inhalation of synthetic surfactant was shown to reduce LIRI, increase arterial oxygen tension and lower levels of oxidative stress after lung transplantation in pigs (88).…”

Lung Surfactant Lipids Provide Immune Protection Against Haemophilus influenzae Respiratory Infection

“…Experiments were done using a synthetic mixture of surfactant phospholipids (PL), in the form of either MLVs or small unilamellar vesicles (SUVs). Surfactant vesicles were composed of dipalmitoylphosphatidylcholine (DPPC), 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG), and palmitic acid (PA) (Avanti Polar Lipids) at weight ratios of 23:10:1.6 as previously reported (37–39). The lipid composition of these vesicles was chosen according to the following criteria: (i) a high DPPC content, which is the main phospholipid constituent of pulmonary surfactant (~50 wt.% of the total surfactant PL); (ii) the presence of an unsaturated anionic phospholipid (POPG), which forms part of lung surfactant (~8–15 wt.%); and (iii) the presence of small amounts of palmitic acid in surfactant (19, 20).…”