title: Effects of inhaled CO administration on acute lung injury in baboons with pneumococcal pneumonia.
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.
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; lfredenburgh@rics.bwh.harvard.edu.
authors: Laura E
authors: LE
authors: Fredenburgh
authors: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, North Carolina;
authors: Bryan D
authors: BD
authors: Kraft
authors: Department of Respiratory Care, Massachusetts General Hospital, Boston, Massachusetts; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts;
authors: Dean R
authors: DR
authors: Hess
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts;
authors: R Scott
authors: RS
authors: Harris
authors: Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina;
authors: Monroe A
authors: MA
authors: Wolf
authors: Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina;
authors: Hagir B
authors: HB
authors: Suliman
authors: Department of Pathology, Duke University Medical Center, Durham, North Carolina;
authors: Victor L
authors: VL
authors: Roggli
authors: Department of Respiratory Care, Duke University Medical Center, Durham, North Carolina;
authors: John D
authors: JD
authors: Davies
authors: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts;
authors: Tilo
authors: T
authors: Winkler
authors: 12th Man Technologies, Garden Grove, California; and.
authors: Alex
authors: A
authors: Stenzler
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts;
authors: Rebecca M
authors: RM
authors: Baron
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts;
authors: B Taylor
authors: BT
authors: Thompson
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medical College, New York, New York.
authors: Augustine M
authors: AM
authors: Choi
authors: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, North Carolina;
authors: Karen E
authors: KE
authors: Welty-Wolf
authors: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, North Carolina; Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; Department of Pathology, Duke University Medical Center, Durham, North Carolina;
authors: Claude A
authors: CA
authors: Piantadosi
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000209:etiology* / Q000628:therapy*; D000280:Administration, Inhalation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000975:Antioxidants / Q000378:metabolism; D002248:Carbon Monoxide / Q000008:administration & dosage*; D002263:Carboxyhemoglobin / Q000378:metabolism; D004195:Disease Models, Animal; D004867:Equipment Design; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D010215:Papio; D011018:Pneumonia, Pneumococcal / Q000097:blood / Q000150:complications* / Q000628:therapy*; D012121:Respiration, Artificial; D012138:Respiratory Therapy / Q000295:instrumentation; D018805:Sepsis / Q000209:etiology / Q000378:metabolism / Q000628:therapy
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin
keywords: Coburn-Forster-Kane equation; Streptococcus pneumoniae; carbon monoxide; drug delivery systems; pneumonia