Matrix Metalloproteinase Inhibitor: Differential Effects on Pulmonary Neutrophil and Monocyte Sequestration Following Cardiopulmonary Bypass

Acute respiratory distress syndrome (ARDS) following cardiopulmonary bypass (CPB), also known as “post-pump” or “post-perfusion syndrome” (PPS), results from sequential priming and activation of neutrophils. We hypothesized that chemically modified tetracycline (CMT-3) an inhibitor of neutrophil matrix metalloproteinase (MMP) and elastase, would prevent PPS. We performed histometric analysis of lung tissue from our porcine PPS model to correlate cellular sequestration and histologic injury with CMT-3 treatment. Methods: Yorkshire pigs were randomized into five groups: Control (n=3); CPB (n=5); femoral-femoral bypass 1 hour; LPS (n=7), Escherichia coli lipopolysaccharide (1μg/kg); CPB+LPS (n=6); and CPB+LPS+CMT (n=5), sequential insults and CMT-3. Protocol histometric analysis defined cellular and tissue components of lung injury. Results: CMT-3 decreased neutrophil sequestration in the CPB+LPS+CMT-3 group (p