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Effects of inhaled CO administration on acute lung injury in baboons with pneumococcal pneumonia
Journal article   Open access   Peer reviewed

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

Laura E Fredenburgh, Bryan D Kraft, Dean R Hess, R Scott Harris, Monroe A Wolf, Hagir B Suliman, Victor L Roggli, John D Davies, Tilo Winkler, Alex Stenzler, …
American journal of physiology. Lung cellular and molecular physiology, Vol.309(8), pp.L834-L846
10/15/2015
DOI: 10.1152/ajplung.00240.2015
PMCID: PMC4609940
PMID: 26320156
url
https://doi.org/10.1152/ajplung.00240.2015View
Published (Version of record) Open Access

Abstract

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 (10(8)-10(9) 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 × 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 ≤ 1 ppm. The COHb level measured at 20 min predicted the 60-min COHb level by the Coburn-Forster-Kane equation with high accuracy. Animals given inhaled CO + antibiotics displayed significantly less ALI at 8 days postinoculation compared with antibiotics alone. Inhaled CO was associated with activation of mitochondrial biogenesis in the lung and with augmentation of renal antioxidative programs. These data support the feasibility of safely delivering inhaled CO gas during mechanical ventilation and provide preliminary evidence that CO may accelerate the resolution of ALI in a clinically relevant nonhuman primate pneumonia model.
 Acute Lung Injury - blood Acute Lung Injury - etiology Acute Lung Injury - therapy Administration, Inhalation Animals Anti-Bacterial Agents - administration & dosage Antioxidants - metabolism Carbon Monoxide - administration & dosage Carboxyhemoglobin - metabolism Disease Models, Animal Equipment Design Humans Kidney - metabolism Lung - pathology Male Papio Pneumonia, Pneumococcal - blood Pneumonia, Pneumococcal - complications Pneumonia, Pneumococcal - therapy Respiration, Artificial Respiratory Therapy - instrumentation Sepsis - etiology Sepsis - metabolism Sepsis - therapy

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