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

We characterised early circulatory and respiratory responses to :lipopolysaccharide from E. coli(LPS, serotype O127:B8) in the isolated, ventilated and perfused rat lung preparation. Lungs were isolated from anaesthetised Wistar rats and perfused with full blood, platelet rich plasma (PRP), platelet poor plasma (PPP) or Krebs-Henseleit solution (KH). LPS (300 mu g/ml) injected into the blood-perfused lung induced a characteristic biphasic response consisting of an immediate, transient decrease in respiratory tidal volume and an increase in pulmonary perfusion pressures followed by a delayed decrease in respiratory tidal,volume; An immediate respiratory/circulatory response to LPS was of considerable magnitude only in full blood-perfused lung whereas the delayed response was fully expressed irrespective whether blood, PRP, PPP or KH was used for the lung perfusion. Immediate respiratory/circulatory response was inhibited by WEB 2170 (100 mu M), a PAF receptor antagonist, and by camonagrel (300 mu M), a TXA(2) synthase inhibitor, but not by MK 571 (100 mu M), a cysteinyl leukotriene receptor antagonist. Delayed respiratory response was inhibited by camonagrel only. In summary, we demonstrated that the immediate coupled respiratory/circulatory response is mediated by blood cell-derived PAF and TXA(2) whereas the delayed uncoupled respiratory response is mediated by lung parenchyma-derived TXA(2).