Surfactant alterations and treatment of lung transplant ischemia-reperfusion injury

This review addresses surfactant alterations and treatment in lung transplant ischemia-reperfusion injury. Lung ischemia-reperfusion injury damages the endogenous surfactant system as a result of the production of reactive oxygen species, proteolytic enzymes and (phospho)lipases. Surfactant is composed of phospholipids and proteins and its main function is to reduce the surface tension inside the alveolus. Impairment of surfactant will cause atelectasis, influx of serum proteins, pulmonary edema, decreased lung compliance and impaired gas exchange. Surfactant therapy restores the quantity and composition of surfactant and reduces the inhibitory effect of serum proteins; other effects are that it serves as an antioxidant and anti-inflammatory agent. Pretreatment may be more beneficial than treatment after the development of lung ischemia-reperfusion injury. However, the cost of surfactant must be weighed against the clinical outcome

In vivo evaluation of the inhibitory capacity of human plasma on exogenous surfactant function

Objective: The adult respiratory distress syndrome (ARDS) and neonatal respiratory distress syndrome (RDS) are characterized by high permeability pulmonary edema which contains plasma-derived proteins inhibiting pulmonary surfactant function. Currently, discussion continues as to what dose of surfactant is required for treatment of these syndromes. Design: The purpose of this study was to investigate the amount of exogenous surfactant needed to overcome the inhibitory components in human plasma. Male adult rats suffering from respiratory failure due to surfactant depletion after whole-lung lavage received human plasma (4 ml/kg body weight) mixed with surfactant at different concentrations, intratracheally. Rats receiving surf

Partial liquid ventilation improves lung function in ventilation-induced lung injury

Disturbances in lung function and lung mechanics are present after ventilation with high peak inspiratory pressures (PIP) and low levels of positive end-expiratory pressure (PEEP). Therefore, the authors investigated whether partial liquid ventilation can re-establish lung function after ventilation-induced lung injury. Adult rats were exposed to high PIP without PEEP for 20 min. Thereafter, the animals were randomly divided into five groups. The first group was killed immediately after randomization and used as an untreated control. The second group received only sham treatment and ventilation, and three groups received treatment with perfluorocarbon (10 mL x kg(-1), 20 mL x kg(-1), and 20 ml x kg(-1) plus an additional 5 mL x kg(-1) after 1 h). The four groups were maintained on mechanical ventilation for a further 2-h observation period. Blood gases, lung mechanics, total protein concentration, minimal surface tension, and small/large surfactant aggregates ratio were determined. The results show that in ventilation-induced lung injury, partial liquid ventilation with different amounts of perflubron improves gas exchange and pulmonary function, when compared to a group of animals treated with standard respiratory care. These effects have been observed despite the presence of a high intra-alveolar protein concentration, especially in those groups treated with 10 and 20 mL of perflubron. The data suggest that replacement of perfluorocarbon, lost over time, is crucial to maintain the constant effects of partial liquid ventilation

Hemodynamic effects of partial liquid ventilation with perfluorocarbon in acute lung injury

Objective: To assess the effect of partial liquid ventilation with perfluorocarbons on hemodynamics and gas exchange in large pigs with induced acute lung injury (ALI). Design: Randomized, prospective, double-control, experimental study. Setting: Experimental intensive care unit of a university. Materials: Eighteen large pigs (50±5 kg body weight) with an average anterior posterior thoracic diameter of 24 cm and induced acute lung injury. Interventions: All animals were surfactant depleted by lung lavage to a PaO2 below 100 mmHg and randomized to receive either perflubron (n=6) or saline (n=6) in five intratracheal doses of 5 ml/kg at 20-min intervals, or no instillation (n=6). Measurements and results: In all animals heart rate, arterial pressures, pulmonary pressures, cardiac output and blood gases were recorded at 20-min intervals. There was no deleterious effect on any hemodynamic parameter in the perflubron group, whereas systolic and mean pulmonary arterial pressure values showed a persistent decrease after the first 5 ml/kg of perflubron, from 48.7±14.1 to 40.8±11.7 mmHg and from 39.7±13.2 to 35.2±12.0 mmHg, respectively. Perflubron resulted in a significant (ANOVA P<0.01), dose-dependent increase in PaO2 values from 86.3±22.4 to a maximum of 342.4±59.4 mmHg at a dose of 25 ml/kg; the other groups showed no significant increase in PaO2. Conclusions: Tracheal instillation of perflubron in induced ALI results in a dose-dependent increase in PaO2 and has no deleterious effect on hemodynamic parameters

Human SP-A and a pharmacy-grade porcine lung surfactant extract can be reconstituted into tubular myelin--a comparative structural study of alveolar surfactants using cryo-transmission electron microscopy.

Cryo-transmission electron microscopy (cryo-TEM) is a rather artefact-free method, well suited to study the alveolar surfactant system. A pharmacy grade porcine lung surfactant extract (HL-10) was mixed with human SP-A and Ringer's solution (for calcium ions), and it was shown by cryo-TEM that the tubular myelin (TM) type of structure was reconstituted. These aggregates were associated to liposomal aggregates, and resulted in macroscopic phase-separation. This phase showed a weak birefringence in the polarising microscope, which is characteristic for a liquid-crystalline type of structure. TM from rabbit lung lavage was also examined, and showed the same periodic arrangement of bilayers as alveolar surface layer from freshly cut rabbit lungs deposited directly on the cryo-TEM grids. The distance between the bilayers of TM was 40-50 nm, and an electron dense material, assumed to be SP-A, was sometimes seen to occur periodically along the bilayers, oriented perpendicularly to the tubuli. The results are consistent with the surface-phase model of the alveolar lining

High-frequency oscillatory ventilation is not superior to conventional mechanical ventilation in surfactant-treated rabbits with lung injury

The aim of this study was to compare high-frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CMV) with and without surfactant in the treatment of surfactant-deficient rabbits. A previously described saline lung lavage model of lung injury in adult rabbits was used. The efficacy of each therapy was assessed by evaluating gas exchange, lung deflation stability and lung histopathology. Arterial oxygenation did not improve in the CMV group without surfactant but increased rapidly to prelavage values in the other three study groups. During deflation stability, arterial oxygenation decreased to postlavage values in the group that received HFOV alone, but not in both surfactant-treated groups (HFOV and CMV). The HFOV group without surfactant showed more cellular infiltration and epithelial damage compared with both surfactant-treated groups. There was no difference in gas exchange, lung deflation stability and lung injury between HFOV and CMV after surfactant therapy. It is concluded that the use of surfactant therapy in combination with high-frequency oscillatory ventilation is not superior to conventional mechanical ventilation in improving gas exchange, lung deflation stability and in the prevention of lung injury, if lungs are kept expanded. This indicates that achieving and maintaining alveolar expansion (i.e. open lung) is of more importance than the type of ventilator

Surfactant therapy restores gas exchange in lung injury due to paraquat intoxication in rats

Paraquat is a weed killer which causes often fatal lung damage in humans and other animals. There is evidence that the pulmonary surfactant system is involved in the pathophysiology of respiratory failure after paraquat intoxication and, therefore, the possible therapeutic effect of intratracheal surfactant administration on gas exchange in rats with progressive lung injury induced by paraquat poisoning was studied. In one g