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* Research Division, Heart Institute (InCor) and LIM 11, University of São Paulo Medical School, São Paulo, Brazil; and Division of Trauma, Department of Surgery, University of California San Diego School of Medicine, San Diego, California 92103-8896
To whom requests for reprints should be addressed at 1 Division of Trauma, 8896, University of California San Diego School of Medicine, 200 West Arbor Drive, San Diego, CA 92103–8896. E-mail: rcoimbra{at}ucsd.edu
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 µm 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. Exp Biol Med 229:684–693, 2004
Key Words: hemorrhagic shock • microcirculation • hypertonic saline • Pentoxifylline • PMN
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  R. J. Cruz Jr, M. M. Yada-Langui, L. F. P. de Figueiredo, S. Sinosaki, and M. R. e Silva The synergistic effects of pentoxifylline on systemic and regional perfusion after hemorrhage and hypertonic resuscitation. Anesth. Analg., May 1, 2006; 102(5): 1518 - 1524. [Abstract] [Full Text] [PDF]
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