Effects of inhaled CO administration on acute lung injury in baboons with pneumococcal pneumonia

Effects of inhaled CO administration on acute lung injury in baboons with pneumococcal pneumonia
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DOI:
10.1152/ajplung.00240.2015
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发表时间:
2015-10-15
影响因子:
4.9
通讯作者:
Piantadosi, Claude A.
Piantadosi, Claude A.
中科院分区:
医学2区
文献类型:
--
作者:
Fredenburgh, Laura E.;Kraft, Bryan D.;Piantadosi, Claude A.

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如果能够开发出安全、循证的剂量策略和与呼吸机兼容的 CO 输送系统,吸入一氧化碳 (CO) 气体对于急性呼吸窘迫综合征患者具有治疗潜力。在这项研究中,我们使用临床相关的肺炎链球菌肺炎狒狒模型来1)测试一种新型的、与呼吸机兼容的CO输送系统; 2)建立安全有效的CO给药方案; 3) 研究 CO 疗法对炎症和急性肺损伤 (ALI) 的局部和全身影响。动物接种肺炎链球菌 (108-109 CFU) (n = 14) 或盐水载体 (n = 5);在肺炎患者子集中 (n = 5),我们在接种后 0、6、24 和/或 48 小时吸入低剂量 CO 气体(100-300 ppm X 60-90 分钟),并连续测量血液碳氧血红蛋白 (COHb) 水平。我们发现,吸入 200 ppm 的 CO 60 分钟具有良好的耐受性,并且可达到环境 CO 水平的 6-8% 的 COHb
Inhaled carbon monoxide (CO) gas has therapeutic potential for patients with acute respiratory distress syndrome if a safe, evidence-based dosing strategy and a ventilator-compatible CO delivery system can be developed. In this study, we used a clinically relevant baboon model of Streptococcus pneumoniae pneumonia to 1) test a novel, ventilator-compatible CO delivery system; 2) establish a safe and effective CO dosing regimen; and 3) investigate the local and systemic effects of CO therapy on inflammation and acute lung injury (ALI). Animals were inoculated with S. pneumoniae (108-109 CFU) (n = 14) or saline vehicle (n = 5); in a subset with pneumonia (n = 5), we administered low-dose, inhaled CO gas (100-300 ppm X 60-90 min) at 0, 6, 24, and/or 48 h postinoculation and serially measured blood carboxyhemoglobin (COHb) levels. We found that CO inhalation at 200 ppm for 60 min is well tolerated and achieves a COHb of 6-8% with ambient CO levels