Hypercapnia via reduced rate and tidal volume contributes to lipopolysaccharide-induced lung injury.
Appreciating that CO2 modifies the chemical reactivity of nitric oxide (NO)-derived inflammatory oxidants, we investigated whether hypercapnia would modulate pulmonary inflammatory responses. Rabbits (n = 72) were ventilated with approximately 7-ml/kg tidal volume for 6 hours. Animals were randomized to one of the following conditions: eucapnia (Pa(CO2) at approximately 35-40 mm Hg), eucapnia + lipopolysaccharide (LPS), eucapnia + LPS + inhaled NO (iNO delivered at approximately 20 ppm), hypercapnia (Pa(CO2) at approximately 60 mm Hg), hypercapnia + LPS, and hypercapnia + LPS + iNO. The hypercapnia + LPS groups compared with groups exposed to eucapnia + LPS displayed significantly increased bronchoalveolar lavage fluid protein concentrations (p < 0.05), lung wet-to-dry ratios (p < 0.05), bronchoalveolar lavage fluid cell counts (p < 0.05), and lung histologic alterations consistent with greater injury. Furthermore, expression of inducible nitric oxide synthase (p < 0.05), tissue myeloperoxidase content (p < 0.05), and formation of lung protein 3-nitrotyrosine derivatives (p < 0.05) was greatest under conditions of hypercapnia + LPS. Groups exposed to hypercapnic conditions without LPS did not manifest these changes. The inhalation of iNO attenuated selected indices of lung injury. We conclude that hypercapnia induced by means of reduced rate and tidal volume amplifies pulmonary inflammatory responses.
Department of Anesthesiology, The University of Alabama at Birmingham, Birmingham, Alabama 35233-6810, USA. john.lang@ccc.uab.edu
John D
JD
Lang
Mario
M
Figueroa
K David
KD
Sanders
Mutay
M
Aslan
Yuliang
Y
Liu
Phillip
P
Chumley
Bruce A
BA
Freeman
D000704:Analysis of Variance; D000818:Animals; D002245:Carbon Dioxide / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D006935:Hypercapnia / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000503:physiopathology; D008070:Lipopolysaccharides; D009569:Nitric Oxide / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D011817:Rabbits; D011897:Random Allocation; D012121:Respiration, Artificial / Q000379:methods*; D012128:Respiratory Distress Syndrome / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D013990:Tidal Volume
D008070:Lipopolysaccharides; D002245:Carbon Dioxide; D009569:Nitric Oxide