title: Different effects of surfactant and inhaled nitric oxide in modulation of inflammatory injury in ventilated piglet lungs.
abstract: Septic acute lung injury (ALI) causes high morbidity and mortality in intensive care service as a result of biotrauma and dysfunction in the lungs and other organ systems. We hypothesized that surfactant and/or inhaled nitric oxide (iNO) may have different effects in modulation of inflammatory injury in septic ALI. Twenty-four healthy, 6-9 kg piglets were anesthetized, and intraperitoneally injected with Escherichia coli, followed by a low tidal volume ventilation until sepsis and ALI developed within 4-6 h. They were then randomly treated in groups (n=6 each) as: control (C), inhaled NO at 10 ppm (NO), surfactant at 100mg/kg (Surf), or both surfactant and iNO (SNO). A normal control group (N) was sham-injected and similarly ventilated. Over the 24 h of treatment period, both Surf, and SNO groups had significantly improved PaO2/FiO2, dynamic compliance and resistance of respiratory system. At 24h, the best alveolar aeration and least protein leakage, the lowest wet-to-dry lung weight ratio and lung injury score were found in SNO. Activity of nuclear factor kappa B (NF-kappaB) and myeloperoxidase, interleukin 8 mRNA expression and melondialdehyde were significantly increased, and IL-10 mRNA decreased, in lung tissue of the C group, but were significantly altered in the SNO group, and moderately altered in either NO or Surf group. We conclude that the effects of lung protection by surfactant and/or iNO in this model may be different in modulation of inflammatory cytokine mRNA expression and activity of NF-kappaB, and iNO did not have adverse effects.
authors.affiliation: Laboratory of Pediatric Respiratory and Intensive Care Medicine, Children's Hospital, Fudan University, 183 Feng Lin Road, Shanghai 200032, People's Republic of China.
authors.forename: Yourong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Chunbao
authors.initials: C
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Gong
authors.forename: Chuanqing
authors.initials: C
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
mesh_terms: D000208:Acute Disease; D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D024202:Electrophoretic Mobility Shift Assay; D004927:Escherichia coli Infections / Q000150:complications; D051523:Fibroblast Growth Factor 7 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008706:Methemoglobin / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D009573:Nitrites / Q000097:blood; D015345:Oligonucleotide Probes / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D011485:Protein Binding / Q000187:drug effects; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D012123:Pulmonary Ventilation; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D012131:Respiratory Insufficiency / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D013552:Swine
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D009566:Nitrates; D009573:Nitrites; D015345:Oligonucleotide Probes; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D051523:Fibroblast Growth Factor 7; D016753:Interleukin-10; D009569:Nitric Oxide; D008315:Malondialdehyde; D008706:Methemoglobin; D009195:Peroxidase