Neutrophil Phenotypic Profiling and Acute Lung Injury in Patients After Cardiopulmonary Bypass (CPB)

Brief Summary

Detailed Description

Acute lung injury (ALI) is frequently associated with the use of extracorporeal circulation during cardiopulmonary bypass (CPB) surgery and develops postoperatively in 2-3% of cardiac surgical patients. Histological evidence shows that CPB increases pulmonary vascular permeability and extravascular lung water content while diminishing pulmonary compliance. Furthermore, some patients can develop acute respiratory distress syndrome, which has a mortality rate of 50-70%. Recruitment of intrapulmonary neutrophils is a characteristic of ALI following CPB. Blood contact with non-physiological surfaces, cooling and rewarming and mechanical shear stress activate neutrophils. The recruitment of activated neutrophils from blood vessels to local tissue involves a chain of well-coordinated events, including adhesion, tethering, rolling and crawling, followed by trans-endothelial and trans-epithelial migration. Activation of sequestered neutrophils causes the release of specific proteolytic enzymes and oxygen free radicals, which leads to increased alveolar-endothelial permeability and parenchymal damage. During CPB, the lungs are almost completely excluded from the systemic circulation, which causes the blood within them to be almost 'static'. Pulmonary tissue hypoxia and re-oxygenation combined with vascular ischemia and reperfusion induce the generation of chemokines, which contributes to subsequent injury by accumulating and entrapping activated neutrophils. The accumuled and entrapped activated neutrophils in the lungs and the subsequent release of toxic substances render the lungs highly susceptible to this damage. However, the mechanism that drives neutrophil migration to the lungs after CPB is not well studied. This study will delineate the mechanisms of neutrophil migration to the lung and subsequent lung injury after CPB.

Primary Outcomes

Secondary Outcomes

• Determine neutrophil functions(2 years)
• Determine chemoattractant levels(2 years)