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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Fredenburgh, LE; Kraft, BD; Hess, DR; Harris, RS; Wolf, MA; Suliman, HB; Roggli, VL; Davies, JD; Winkler, T; Stenzler, A; Baron, RM; Thompson, BT; Choi, AM; Welty-Wolf, KE; Piantadosi, CA

Published Date

  • October 15, 2015

Published In

Volume / Issue

  • 309 / 8

Start / End Page

  • L834 - L846

PubMed ID

  • 26320156

Pubmed Central ID

  • 26320156

Electronic International Standard Serial Number (EISSN)

  • 1522-1504

Digital Object Identifier (DOI)

  • 10.1152/ajplung.00240.2015

Language

  • eng

Conference Location

  • United States