title: Therapeutic hypercapnia and ventilation-perfusion matching in acute lung injury: low minute ventilation vs inspired CO2.
abstract: OBJECTIVE
  Hypercapnic acidosis has antiinflammatory effects in animal models of acute lung injury (ALI) and improves ventilation-perfusion (V/Q) matching in normal lungs. The effect of hypercapnia on V/Q matching in ALI is conflicting. Hypercapnic acidosis produced by reduced tidal volumes (Vts) was associated with an increased shunt fraction (QS/QT) in patients with ALI compared with control subjects. Vt differences between groups make the assessment of hypercapnic acidosis on V/Q matching difficult. Adding CO2 to the inhaled gas allows the comparison of gas exchange under identical Vt conditions. We hypothesized the presence of hypercapnic acidosis from inspired carbon dioxide (ICD) would improve gas exchange in ALI and would be superior to that of low minute ventilation (LVe) produced by reduced respiratory rate, rather than Vt.
  
  
  METHODS
  University laboratory study of anesthetized New Zealand White rabbits.
  
  
  METHODS
  Assessment of V/Q relationships using the multiple inert gas elimination technique was performed in 10 saline solution-lavaged animals, which were ventilated with 6 mL/kg Vts and a positive end-expiratory pressure of 8 cm H2O. Each rabbit was studied while it was in eucapnia, followed by hypercapnia (Pa(CO2), 95 to 100 mm Hg) induced by LVe from decreased respiratory rate and by 10% ICD, in random order.
  
  
  RESULTS
  The Pa(O2) was greater in ICD and LVe compared to eucapnia, but no significant differences in alveolar-arterial oxygen pressure difference or Pa(O2)/fraction of inspired oxygen ratio occurred. LVe statistically reduced the mean V/Q distributions compared with ICD and eucapnia. Log SDs of ventilation and combined retention and excretion curves of the dispersion index were both increased during LVe, indicating the presence of unfavorable changes in ventilation distribution. Neither LVe nor ICD altered the QS/QT.
  
  
  CONCLUSIONS
  LVe slightly impairs overall gas exchange and ventilation distribution, but does not increase QS/QT compared with eucapnia and ICD. While ICD does not significantly improve gas exchange, it may be superior to LVe in achieving the antiinflammatory effects of "therapeutic" hypercapnia, since it does not adversely alter gas exchange and has the potential to make the lung more uniformly acidotic.
authors.affiliation: Department of Medicine, University of Tennessee, 956 Court Ave, Room H314, Memphis, TN 38163, USA. ssincla1@utmem.edu
authors.forename: Scott E
authors.initials: SE
authors.lastname: Sinclair
authors.forename: David A
authors.initials: DA
authors.lastname: Kregenow
authors.forename: Ian
authors.initials: I
authors.lastname: Starr
authors.forename: Carmel
authors.initials: C
authors.lastname: Schimmel
authors.forename: Wayne J E
authors.initials: WJ
authors.lastname: Lamm
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hlastala
authors.forename: Erik R
authors.initials: ER
authors.lastname: Swenson
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006935:Hypercapnia / Q000378:metabolism*; D008297:Male; D011659:Pulmonary Gas Exchange; D011817:Rabbits; D012121:Respiration, Artificial / Q000379:methods; D012128:Respiratory Distress Syndrome / Q000378:metabolism / Q000628:therapy*; D014692:Ventilation-Perfusion Ratio / Q000502:physiology
chemical_list: D002245:Carbon Dioxide