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. CONCLUSION: 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.
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. CONCLUSION: 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.
Authors: Seiko F Okada; Robert A Nicholas; Silvia M Kreda; Eduardo R Lazarowski; Richard C Boucher Journal: J Biol Chem Date: 2006-06-05 Impact factor: 5.157
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