Adenosine triphosphate is released during injurious mechanical ventilation and contributes to lung edema.
BACKGROUND
Extracellular nucleotides mediate many cellular functions and are released in response to mechanical stress in vitro. It is unknown whether adenosine triphosphate (ATP) is released in vivo during mechanical ventilation (MV). We hypothesized that stress from high-pressure MV would increase airway ATP, contributing to MV-associated lung edema.


METHODS
Rats were randomized to nonventilated control (n = 6) or 30 minutes of MV with low (15 cm H(2)0, n = 7) or high (40 cm H(2)0, n = 6) pressure. Additional groups received intratracheal ATP (n = 7) or saline (n = 7) before low-pressure MV.


RESULTS
Low-pressure MV did not affect lung edema or bronchoalveolar lavage (BAL) ATP levels. In contrast, high-pressure MV significantly increased BAL ATP and produced alveolar edema; lactate dehydrogenase was unchanged. Intratracheal ATP administration significantly increased lung water during low-pressure MV.


CONCLUSIONS
High-pressure MV increases BAL ATP concentration without altering lactate dehydrogenase, suggesting that release is not from cell lysis. Intratracheal ATP increases lung water, implicating nucleotides in MV-associated lung edema.
Rich
Preston B
PB
Department of Surgery, Univeristy of North Carolina School of Medicine, Chapel Hill, 27599-7228, USA. prich@med.unc.edu
Douillet
Christelle D
CD
Mahler
Simon A
SA
Husain
Syed Adil
SA
Boucher
Richard C
RC
D000255:Adenosine Triphosphate / Q000009:adverse effects* / Q000032:analysis*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D004195:Disease Models, Animal; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008297:Male; D009195:Peroxidase / Q000032:analysis; D011175:Positive-Pressure Respiration / Q000009:adverse effects*; D011654:Pulmonary Edema / Q000209:etiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology*
D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase