title: Pulmonary artery perfusion with anti-tumor necrosis factor alpha antibody reduces cardiopulmonary bypass-induced inflammatory lung injury in a rabbit model.
abstract: Inflammatory lung injury is one of the main complications associated with cardiopulmonary bypass (CPB). Tumor necrosis factor-α (TNF-α) is one of the key factors mediating the CPB-induced inflammatory reactions. Our previous studies have shown that endotracheal administration of anti-tumor necrosis factor-α antibody (TNF-α Ab) produces some beneficial effects on lung in a rabbit CPB model. In this study, we further examined the effects of pulmonary artery perfusion with TNF-α Ab (27 ng/kg) on lung tissue integrity and pulmonary inflammation during CPB and investigated the mechanism underlying the TNF-α Ab-mediated effects in a rabbit model of CPB. Our results from transmission electron microscopy showed that the perfusion with TNF-α Ab alleviated CPB-induced histopathological changes in lung tissue. The perfusion with TNF-α Ab also prevented CPB-induced pulmonary edema and improved oxygenation index. Parameters indicating pulmonary inflammation, including neutrophil count and plasma TNF-α and malondialdehyde (MDA) levels, were significantly reduced during CPB by pulmonary artery perfusion with TNF-α Ab, suggesting that the perfusion with TNF-α Ab reduces CPB-induced pulmonary inflammation. We further investigated the molecular mechanism underlying the protective effects of TNF-α Ab on lung. Our quantitative RT-PCR analysis revealed that pulmonary artery perfusion with TNF-α Ab significantly decreased TNF-α expression in lung tissue during CPB. The apoptotic index in lung tissue and the expression of proteins that play stimulatory roles in apoptosis pathways including the fas ligand (FasL) and Bax were markedly reduced during CPB by the perfusion with TNF-α Ab. In contrast, the expression of Bcl-2, which plays an inhibitory role in apoptosis pathways, was significantly increased during CPB by the perfusion with TNF-α Ab, indicating that the perfusion with TNF-α Ab significantly reduces CPB-induced apoptosis in lung. Thus, our study suggests that pulmonary artery perfusion with TNF-α Ab might be a promising approach for attenuating CPB-induced inflammatory lung injury.
authors.affiliation: Department of Cardiac Surgery, Beijing An Zhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Cardiac Surgery, Beijing An Zhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Mingxin
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Cardiac Surgery, Beijing An Zhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Cardiac Surgery, Beijing An Zhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Cardiac Surgery, Beijing An Zhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Chengxiong
authors.initials: C
authors.lastname: Gu
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D005260:Female; D008297:Male; D010477:Perfusion; D011183:Postoperative Complications / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D011651:Pulmonary Artery / Q000187:drug effects* / Q000473:pathology; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha