Published ahead of print on September 23, 2004, doi:10.1165/rcmb.2004-0177OC
© 2005 American Thoracic Society DOI: 10.1165/rcmb.2004-0177OC Mechanical Ventilation Alters Airway Nucleotides and Purinoceptors in Lung and Extrapulmonary OrgansDepartments of Surgery and Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina Correspondence and requests for reprints should be addressed to Preston B. Rich, M.D., Department of Surgery, Section of Critical Care, University of North Carolina at Chapel Hill, School of Medicine, Medical School Wing D, Room 186, CB#7228, Chapel Hill, NC 27599-7228. E-mail: prich{at}med.unc.edu Extracellular nucleotides are stress-responsive ligands that mediate a variety of cellular processes via purinoceptors. We hypothesized that mechanical ventilation (MV) would alter the extracellular adenyl-nucleotide profile and purinoceptor expression in lung and extrapulmonary tissues. Twenty-eight rats were randomized to: (i) unventilated control animals; (ii) tidal volume (VT; 6 ml/kg); (iii) VT (6 ml/kg) and positive end-expiratory pressure (PEEP; 5 cm H20); (iv) VT (12 ml/kg); or (v) VT (12 ml/kg) and PEEP (5 cm H20). Bronchoalveolar lavage (BAL) was analyzed for adenyl-nucleotides. Pulmonary, hepatic, and renal tissues were assessed for P2Y4, P2Y6, P2X7, A3, and A2b receptor expression by real-time reverse transcriptase–polymerase chain reaction and Fas/Fas ligand mRNA was quantified in the lung. MV produced volume-dependent changes in BAL nucleotides; AMP and adenosine increased, whereas ATP and ADP proportions decreased. Large-volume MV increased A2b mRNA and decreased P2X7 in the lung; mRNA changes in lung Fas ligand paralleled P2X7. PEEP normalized BAL nucleotide profiles and A2b expression. Injurious MV reduced hepatic and renal P2X7 mRNA; PEEP normalized these levels in both tissues. Large-volume MV also decreased renal A2b mRNA. MV alters the BAL adenyl-nucleotide profile and purinoceptor patterns in lung, liver, and kidney. PEEP normalizes the BAL nucleotide profile and receptor patterns in lung and extrapulmonary tissues.
Key Words: mechanical ventilation • nucleotide • purinoceptor • ventilator-induced lung injury This article has been cited by other articles:
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