The Role of a High Cholesterol Diet on Surfactant Biophysics during Acute Lung Injury

Background Pulmonary surfactant is mixture of phospholipid (85%), surfactant proteins (~10%), and neutral lipids, predominately cholesterol (~5%), vital for normal respiratory function. Surfactant's biophysical function is to reduce lung surface tension, especially during exhalation (compression) where surface tensions reach near 0mN/m values, thereby helping to maintain normal pulmonary compliance. However, in acute lung injury, characterized by reduced arterial oxygenation, dysfunction of the surfactant system contributes to impaired respiratory function. Recent studies have shown that supra‐physiological levels of cholesterol in surfactant contributes to impaired surface tension reduction of surfactant from injured lungs. It is unknown if elevated serum cholesterol levels can contribute to elevated cholesterol in surfactant and thereby play a predisposing role in the development of more severe acute lung injury through surfactant biophysical impairment. It was hypothesized that rats fed a high cholesterol diet would have more severely impaired surfactant biophysical function, due to increased cholesterol incorporation into newly secreted surfactant, compared to standard diet counterparts. Methods Rats were randomized to receive either a standard diet or a high cholesterol diet for 17 – 20 days. A blood sample was taken to confirm serum cholesterol levels attributed to each diet. Subsequently, rats were repeatedly lavaged to remove surfactant, inducing acute lung injury and fresh surfactant secretion. Following 2 hours of mechanical ventilation, during which arterial oxygenation was monitored, extracellular surfactant was isolated by lavage and surfactant phospholipid and cholesterol content was quantified. Surfactant was concentrated to 2mg/ml and biophysical function during 20 dynamic compression/expansion cycles was assessed using a constrained sessile drop surfactometer. Minimum surface tension during each compression cycle was the primary indicator of surfactant biophysical function. Results The results showed no difference in arterial oxygenation following surfactant depleted lung injury and ventilation between rats fed a standard diet and rats fed a high cholesterol diet. Additionally there was no difference in phospholipid or cholesterol content in isolated surfactant from rats fed either diet. Interestingly, surfactant isolated from rats fed a high cholesterol diet did have a significantly decreased ability to reach low surface tensions during compression compared to rats fed a standard diet. This was observed particularly at latter compression cycles which are more representative of the repeated compression/expansion environment surfactant is exposed to in the lung. Conclusion In conclusion, contrary to the hypothesis, a high cholesterol diet did not predispose to more severe lung injury, or increased surfactant cholesterol content during surfactant depleted lung injury. However the high cholesterol diet did produce a significant impairment in minimum surface tension reduction, potentially due to other diet induced changes to surfactant such as alterations to other lipid species composing surfactant. Support or Funding Information Sources of Funding : Canadian Institutes of Health Research

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