Does the timing of hypertonic saline resuscitation affect its potential toprevent lung damage?

Hypertonic saline (HS) resuscitation has been reported to prevent lung dama ge by suppressing neutrophil activation in animal models. Data on the effec tiveness of HS to prevent organ damage in the clinical setting are inconsis tent. We investigated whether the timing of HS administration relative to n eutrophil activation could affect its potential to block neutrophil respons es. Different likely clinical circumstances were simulated in vitro by expo sing human neutrophils to HS at different time points before and after acti vation with N-formyl-methionyl-leucyl-phenylalanine (fMLP). The in vivo eff ect of using HS as a secondary resuscitation fluid was determined with a mo use model of hemorrhage. BALB/c mice were hemorrhaged (40 +/- 5 mmHg) for 1 h and partially resuscitated with HS or Lactated Ringer's (LR) 20 min befo re completing resuscitation with LR or HS, respectively. Neutrophil activat ion parameters were determined 2 h after complete resuscitation and lung da mage was assessed after 24 h. The length of exposure to physiologically rel evant HS levels (20 mM) determined the suppressive effect on in vitro neutr ophil superoxide formation. HS treatment caused a transient state of suppre ssion during which neutrophil activation was suppressed; however, HS was un able to suppress cells that were stimulated with fMLP before HS was added. Accordingly, in viva lung damage was greater in animals that received HS af ter they had been partially resuscitated with LR compared to mice that rece ived HS before LR (P < 0.05). We conclude that timing of exposure to HS aff ects neutrophil responses in vitro and may reduce the potential of HS resus citation to prevent lung injury in vivo.