Infection-induced lung injury is worsened after renal buffering of hypercapnic acidosis.
OBJECTIVE
Prolonged hypercapnia is commonly encountered during the treatment of acute respiratory distress syndrome and acute respiratory failure attributable to other causes with protective ventilation strategies. In these circumstances, compensatory renal buffering returns pH to normal establishing a condition of buffered hypercapnia. It is also common intensive care practice to correct the pH more rapidly using bicarbonate infusions. Although it is well-established that hypercapnic acidosis has potent anti-inflammatory and protective effects, the effect of buffered hypercapnia on acute lung injury and acute respiratory distress syndrome is unknown. We therefore wished to determine the effects of buffered hypercapnia on acute lung injury induced by endotoxin or Escherichia coli infection in vivo.


METHODS
Prospective, randomized animal study.


METHODS
University research laboratory.


METHODS
Adult male Sprague-Dawley rats.


METHODS
We established buffered hypercapnia by exposing rats to a hypercapnic environment for 3 days before the induction of lung injury. Buffered hypercapnia rats (initial pH >7.35, FiCO2 = 0.05) and normocapnic controls (initial pH >7.35, FiCO2 = 0.00) were then anesthetized, mechanically ventilated, and lung injury induced by intra-tracheal inoculation of endotoxin (series I) or Escherichia coli (series II).


RESULTS
Buffered hypercapnia significantly increased both endotoxin and Escherichia coli-induced lung injury when compared to normocapnic controls, as assessed by arterial oxygenation, lung compliance, pro-inflammatory pulmonary cytokine concentrations, and measurements of structural lung damage. In additional in vitro experiments buffered hypercapnia did not alter neutrophil phagocytosis ability but did impaired epithelial wound healing.


CONCLUSIONS
Our results demonstrate that infection-induced injury in vivo is worsened after renal buffering of hypercapnic acidosis independently of any changes in tidal volume. These findings have important implications for our understanding of the pathogenesis of infection-induced lung injury during the use protective ventilation strategies that permits buffered hypercapnia and during infective exacerbations of chronic lung diseases associated with sustained hypercapnia.
Nichol
Alistair D
AD
School of Medicine and Medical, Conway Institute, University, College Dublin, Ireland.
O'Cronin
Donall F
DF
Howell
Katherine
K
Naughton
Finola
F
O'Brien
Sorca
S
Boylan
John
J
O'Connor
Clare
C
O'Toole
Daniel
D
Laffey
John G
JG
McLoughlin
Paul
P
D000142:Acidosis, Respiratory / Q000150:complications / Q000188:drug therapy*; D055371:Acute Lung Injury / Q000150:complications* / Q000382:microbiology; D000818:Animals; D002021:Buffers; D004731:Endotoxins / Q000009:adverse effects; D004927:Escherichia coli Infections / Q000150:complications*; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000150:complications*; D066298:In Vitro Techniques; D008297:Male; D009504:Neutrophils; D010587:Phagocytosis; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017693:Sodium Bicarbonate / Q000008:administration & dosage; D014945:Wound Healing
D002021:Buffers; D004731:Endotoxins; D017693:Sodium Bicarbonate