Effects of pulmonary artery perfusion with urinary trypsin inhibitor as a lung protective strategy under hypothermic low-flow cardiopulmonary bypass in an infant piglet model

Abstract

Objective:

This study aimed to evaluate the effects of pulmonary artery perfusion with a urinary trypsin inhibitor (UTI) as a lung protective strategy in order to provide an experimental basis for immature lung clinical protective strategies on deep hypothermia with low-flow (DHLF) cardiopulmonary bypass (CPB)-induced pulmonary injury in an infant piglet model.

Methods:

The piglets (n=15), aged 18.7±0.3 days, weight 4.48±0.21kg, were randomly divided into 3 groups, with 5 piglets in each group: the control group, the pulmonary artery perfusion without UTI group (Group P) and the pulmonary artery perfusion with UTI group (Group U). The levels of the cytokines tumour necrosis factor-α, myeloperoxidase, malondialdehyde and interleukin-10 (TNF-α, MPO, MDA and IL-10) in pulmonary venous serum and lung tissue and the activity of NF-kappa B in lung tissue were measured by enzyme-linked immunosorbent assay (ELISA) and electrophoresis mobility shift assay (EMSA), respectively.

Results:

After DHLF-CPB, all of the piglets demonstrated a state of lung injury as a deterioration of lung function indices, lung injury scores, pulmonary ultrastructure changes, expression of TNF-α, MPO, MDA and IL-10 and the activities of nuclear factor-kappa B (NF-κB), while pulmonary artery perfusion with UTI significantly ameliorated lung function and histopathological changes, with greatly decreased serum levels of TNF-α and MPO compared to the other two groups. Also, we found an increase in the level of IL-10 in Group U lungs compared with that in Group P lungs, which correlated with a strong inhibition in the activity of NF-κB.

Conclusion:

Pulmonary artery perfusion with UTI ameliorated the DHLF-induced immature pulmonary injury in the lungs via a reduction of pro-inflammatory cytokine expression and up-regulated levels of IL-10 by inhibiting the activity of NF-κB.

Keywords

deep hypothermia with low flow urinary trypsin inhibitor pulmonary artery perfusion nuclear factor kappa B immature lung protection

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