Biphasic response to lipopolysaccharide from E-coli in the isolated ventilated blood-perfused rat lung

We characterised early circulatory and respiratory responses to :lipopolysa ccharide from E. coli(LPS, serotype O127:B8) in the isolated, ventilated an d perfused rat lung preparation. Lungs were isolated from anaesthetised Wis tar rats and perfused with full blood, platelet rich plasma (PRP), platelet poor plasma (PPP) or Krebs-Henseleit solution (KH). LPS (300 mu g/ml) inje cted into the blood-perfused lung induced a characteristic biphasic respons e consisting of an immediate, transient decrease in respiratory tidal volum e and an increase in pulmonary perfusion pressures followed by a delayed de crease in respiratory tidal,volume; An immediate respiratory/circulatory re sponse to LPS was of considerable magnitude only in full blood-perfused lun g whereas the delayed response was fully expressed irrespective whether blo od, PRP, PPP or KH was used for the lung perfusion. Immediate respiratory/c irculatory response was inhibited by WEB 2170 (100 mu M), a PAF receptor an tagonist, and by camonagrel (300 mu M), a TXA(2) synthase inhibitor, but no t by MK 571 (100 mu M), a cysteinyl leukotriene receptor antagonist. Delaye d respiratory response was inhibited by camonagrel only. In summary, we dem onstrated that the immediate coupled respiratory/circulatory response is me diated by blood cell-derived PAF and TXA(2) whereas the delayed uncoupled r espiratory response is mediated by lung parenchyma-derived TXA(2).