We have previously shown that
lung injury following fluid
resuscitation either with hypertonic saline (HS) or
lactated Ringer's (LR) plus
pentoxifylline (PTX) attenuated
acute lung injury when compared with LR
resuscitation. The objective of the present study is to determine whether our previous observations are accompanied by changes in polymorphonu-clear leukocyte (PMN) behavior. To study this, PMN-endothelial cell interactions, microcirculatory blood flow, lung histology, lung PMN infiltration (MPO,
Myeloperoxidase), and lung intra-cellular adhesion molecule-1 (ICAM-1) expression were assessed in a controlled
hemorrhagic shock model followed by LR, HS, and LR+PTX
resuscitation in rodents. Rats (240-300 g) were bled to a mean arterial pressure (MAP) of 35 mm Hg for 1 hr and then randomized into three groups: HS (7.5% NaCl, 4 ml/kg); LR (3x shed blood); and LR+PTX (25 mg/kg). Additionally, total shed blood was reinfused. A
sham group underwent no
shock and no treatment. The internal spermatic fascia was exteriorized and the microcirculation was observed by closed-circuit TV coupled to a microscope, 2 and 6 hrs
after treatment. The number of leukocytes sticking to the venular endothelium was determined 2 hrs after fluid
resuscitation. Microcirculatory blood flow was measured by an optical Doppler velocimeter. Lung histology and lung MPO immunostaining were assessed at 6 hrs, and lung
ICAM-1 expression was determined by immunostaining at 2 hrs following fluid
resuscitation. Two hours
after treatment, HS (1.4 +/- 0.4), LR+PTX (1.7 +/- 0.3), and
sham (0.4 +/- 0.2) groups presented significant reductions in leukocyte adherence (cells/100 microm venule length), compared with the LR group (4.0 +/- 0.9, P < 0.05). No differences were observed 6 hrs
after treatment on leukocyte adherence and microcirculatory blood flow.
ICAM-1 expression was significantly higher in LR-treated animals compared with the HS, LR+PTX, and
sham groups (P < 0.01). PMN infiltration and overall
lung injury were significantly attenuated by HS and LR+PTX. These results support earlier studies that indicated the potential application of HS and PTX in shock therapy and the increase in PMN-endothelial cell interaction and
lung injury after LR
resuscitation.