Ischemic and endotoxin pre-conditioning reduce lung reperfusion injury-induced surfactant alterations.

Background: Pulmonary ischemia/reperfusion injury represents a common clinical phenomenon after lung transplantation, pulmonary embolism, and cardiac surgery with extracorporeal circulation. We investigated the influence of ischemic and endotoxin pre-conditioning on gas exchange and surfactant properties in a canine model of ischemia/reperfusion injury.

Methods: Twenty-six foxhounds underwent 3 hours of warm ischemia of the left lung, followed by 8 hours of reperfusion. Ischemic pre-conditioning was performed for either 5 minutes (IPC-5) or by 2 10-minute ischemic periods (IPC-10), before ischemia. For endotoxin pre-conditioning, dogs were pre-treated by a daily intravenous application of increasing amounts of endotoxin for 6 days. No pre-conditioning was performed in the controls. Bronchoalveolar lavage was performed before ischemia/reperfusion injury (baseline) and after the 8-hour reperfusion period in the non-injured right and in the reperfused left lung. Bronchoalveolar lavage fluids were analyzed for the phospholipid-protein ratio, the content of large surfactant aggregates, the phospholipid and neutral lipid profile, the surfactant protein (SP) content, and for biophysical activity.

Results: Severe surfactant alterations were observed in the ischemia/reperfusion-injured left lung, with increased protein concentrations and depressed concentrations of large surface aggregates, SP-B, dipalmitoylated phosphatidylcholine, and phosphatidylglycerol. Endotoxin pre-conditioning and IPC-5 were both capable of greatly preventing the ischemia/reperfusion injury-related deterioration of surfactant properties. IPC-10 exerted no effects. Endotoxin pre-conditioning and IPC-5, but not IPC-10, also prevented loss of gas exchange.

Conclusions: Ischemic and endotoxin pre-conditioning may protect against impairment of gas exchange in ischemia/reperfusion injury by restoring physiological surfactant properties.