The Research On Correlation Between Matrix Metalloproteinase-9, Its Inhibitor And Acute Lung Injury After Cardiopulmonary Bypass In Infants

Background: Acute lung injury (ALI) is one of the main complications and one of the main causes of death after cardiopulmonary bypass (CPB) in infants. The pathogenesis of ALI after CPB has not clearly elucidated in infants. Matrix metalloproteinase-9 (MMP-9) is one kind of zinc ion dependent proteinase, which can degrade type IV collagen. Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) is the endogenous inhibitor of MMP-9 in tissue, which can inhibit the activity of MMP-9, and they keep balance between each other under physiological conditions. Previous study in a swine model demonstrated that a rise of MMP-9 in bronchoalveolar lavage fluid was associated with ALI after CPB.Objectivities: To observe dynamic change of plasma MMP-9 and TIMP-1 and approach the effects of MMP-9 and TIMP-1 in occurrence and development of ALI in infants after CPB.Methods: Systemic plasma MMP-9 and TIMP-1 were measured by standard enzyme-linked immunosorbent assay (ELISA) in randomly selected 24 left-to-right shunt congenital heart disease infants who underwent open heart operations at pre-CPB, releasing the cross clamp, termination of CPB, and 1hour, 3, 6 and 24 hours after CPB. MMP-9 mRNA within leucocytes was quantified by retro-transcription polymerase chain reaction (RT-PCR) at pre-CPB, termination of CPB, and 6 and 24 hours after CPB. Arterial-alveolar gradient of oxygen tension (AaDO₂), respiratory index (RI) and oxygen index (OI) were measured at pre-CPB, termination of CPB, and lhour, 3 and 6 hours after CPB. Spearman correlation analysis was utilized to define the correlation between MMP-9 concentration, the ratio MMP-9/TIMP-1 and parameters of lung function (AaDO₂, RI and OI).Results: Plasma MMP-9 concentration significantly increased at lhour, 3, 6 and 24 hours after CPB (P < 0.01) as compared with pre-CPB. On the contrary, plasma TIMP-1 concentration significantly decreased at lhour, 3, 6 and 24 hours after CPB (P < 0.01) as compared with pre-CPB. The ratio MMP-9/TIMP-1 significantly increased at lhour, 3, 6 and 24 hours after CPB (P < 0.01) as compared with pre-CPB, and it reached maximum at 3 hours after CPB. Quantity of MMP-9 mRNA within leucocytes significantly increased at termination of CPB, and 6 and 24 hours after CPB (P < 0.01) as compared with pre-CPB. AaDCh and RI significantly increased after CPB (P < 0.01) as compared with pre-CPB, whereas OI significantly decreased (P < 0.01). MMP-9 concentration was significantly correlated with RI (r = 0.25, P = 0.016) and OI (r = - 0.24, P = 0.02), and the ratio MMP-9/TIMP-1 was significantly correlated with RI (r = 0.25, P = 0.016) and OI (r = - 0.24, P = 0.02) during peri-CPB.Conclusions: Plasma concentration of MMP-9 and leucocyte content of MMP-9 mRNA significantly increase after cardiac surgery with CPB in infants, whereas plasma concentration of TIMP-1 significantly decreases. Plasma concentration and activity of MMP-9 are correlated with parameters indicative of ALI after CPB.