Prevention by granulocyte depletion of endotoxin-induced adult respiratory distress syndrome. An experimental study in pigs.

To see whether circulating granulocytes are of importance in mediating endotoxin-induced pulmonary failure with similar characteristics to the human adult respiratory distress syndrome (ARDS), we made pigs granulocytopenic by injecting hydroxyurea via a central venous line for 10 days. The circulating granulocyte count decreased by 95% prior to the start of the continuous (6 h) endotoxin infusion (n = 8), whereas pigs sham-infused for 10 days had a normal granulocyte count before starting the continuous endotoxin infusion (n = 8). Four granulocyte depleted pigs served as controls and received physiological saline instead of endotoxin. No physiological changes occurred in controls during the observation period of 6 h and all animals survived. Granulocyte depletion in response to endotoxin was associated with significantly attenuated pulmonary hypertension, significantly better preservation of cardiac output, significantly better maintained arterial oxygenation and a significantly smaller increase in extravascular lung water throughout the observation period as compared with non-granulocytopenic animals. Seven out of 8 granulocytopenic animals survived the observation period as against 4 out of 8 in non-granulocytopenic animals. Although one should be extremely careful in applying experimental results to the clinical situation, our findings might support the potential use of agents which interfere with granulocyte activation in septic-induced ARDS.