Different effects of surfactant and inhaled nitric oxide in modulation of inflammatory injury in ventilated piglet lungs.
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.
Zhu
Yourong
Y
Laboratory of Pediatric Respiratory and Intensive Care Medicine, Children's Hospital, Fudan University, 183 Feng Lin Road, Shanghai 200032, People's Republic of China.
Guo
Chunbao
C
Cao
Lei
L
Gong
Xiaohui
X
Wang
Chuanqing
C
Sun
Bo
B
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
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