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Background: To investigate the effects of different resuscitation fluids on acute lung injury in a rat model of uncontrolled hemorrhagic shock (HS) followed by mimicked infection., Methods: Sixty Sprague-Dawley rats were randomly assigned to one of the five groups (n = 12 per group) to receive the following treatments: (1) control group (group C), surgery, no hemorrhage, and no resuscitation; (2) no fluid resuscitation group; (3) lactated Ringer's solution group; (4) 7.5% hypertonic saline (HTS) group; and (5) hydroxyethyl starch group (group HES). All experimental groups were subjected to three phases: phase I entailed massive hemorrhage with a mean arterial pressure of 35 mm Hg to 40 mm Hg for 60 minutes by tail amputation and followed by mimicked infection by intratracheal administration of lipopolysaccharide 2 mg/kg. The animals in each group were then partially resuscitated with the fluid assigned to the group. Phase II of 60 minutes commenced at tail ligation, involved hemostasis, and return of all the blood initially shed. Phase III was an observation phase with no any further treatment and lasted for 3.5 hours. The survival rate at the end of the phase III was recorded. After phase III, arterial blood gases were recorded. The wet to dry lung weight ratio, pulmonary microvascular permeability, the expression of transforming growth factor (TGF)-beta1, and Smad2 were determined. The lung histology was also assessed., Results: HES and HTS solutions were more effective than no fluid resuscitation and lactated Ringer's solution in reducing the detrimental effects of HS and infection on the lungs, as seen by the significantly lower pulmonary microvascular permeability and wet to dry lung weight ratio, the improved arterial blood gases and lower levels of TGF-beta1and Smad2 expression in lung tissues. These beneficial effects were most pronounced in the group HES., Conclusions: This study demonstrated that resuscitation with HTS and especially with HES could reduce lung tissue damage and pulmonary edema after severe uncontrolled HS. The TGF-beta1/Smad2 signaling pathway might play a key role in regulation of pulmonary permeability and formation of pulmonary edema in a rat model of uncontrolled HS and infection.

Objective: To investigate the effects of different fluid resuscitation regimes on lung injury and expression of pulmonary aquaporin 1 (AQP1) and AQP5 in rats with uncontrolled hemorrhagic shock., Methods: Sixty Sprague-Dawley (SD) rats were randomly assigned to the following five groups: control group (C group), no fluid resuscitation group (NF group), lactated Ringer's solution group (LRS group), 7.5%NaCl group (HS group) and hydroxyethyl starch group (hydroxyethyl starch 130/0.4, HES group). A four-phased uncontrolled hemorrhagic shock model was reproduced. Uncontrolled hemorrhagic shock phase began with blood withdrawal extended over 15 minutes, in which animals were subjected to massive hemorrhage [mean arterial pressure (MAP)=40 mm Hg (1 mm Hg=0.133 kPa)] for 60 minutes and followed by intratracheal lipopolysaccharide 2 mg/kg and continuous bleeding with amputation of the tail. Then, animals were partially resuscitated with LRS of 3 times the volume of shed blood (LRS group), followed by a bolus dose of 4 ml/kg body weight of 7.5%NaCl (HS), or hydroxyethyl starch (a volume equal to that of the shed blood), respectively, during different fluid resuscitation regimes. After that, comprehensive resuscitation phase of 60 minutes began with hemostasis, and transfusion of all the shed blood plus same amount of normal saline. Observation phase was continued for 3.5 hours. At the end the experiment, the lung tissue was sampled to measure wet-to-dry lung weight ratio (W/D), and the expression of AQP1 and AQP5 were determined with immunohistochemistry. The paraffin-embedded lungs were stained with hematoxylin and eosin for pathological analysis., Results: When compared with NF and LRS groups, the lung W/D ratio was significantly decreased, and the shock induced decreased expression of AQP1 and AQP5 in lung tissue were attenuated in HES group, but these beneficial effects were blunted in the HS group., Conclusion: Uncontrolled hemorrhagic shock may induce lung injury and pulmonary edema as well as down regulation of the expression of AQP1 and AQP5 in rats. Resuscitation with hypertonic fluids, especially with HES, can reduce lung damage and pulmonary edema in this kind of shock. The cause may be due in part to maintenance of the expression of AQP1 and/or AQP5 in the lung. Pulmonary AQP1 and AQP5 play an important role in fluid transportation.

Objective: To investigate the changes in pulmonary transforming growth factor-beta1 (TGF-beta1)/smad2 signaling pathway in pulmonary injury as a result of hemorrhagic shock followed by lipopolysaccharide challenge., Methods: Twenty-four Sprague-Dawley (SD) rats were randomly assigned to the following two groups: sham operation group (sham group, surgery, no hemorrhage and no resuscitation), and two-hit model group (HS group), each n=12. Three-phased uncontrolled hemorrhagic shock model was reproduced in rats. Hemorrhagic shock phase I began with blood withdrawal over 15 minutes, i.e. animals were subjected to massive hemorrhage [mean arterial pressure (MAP)=35-40 mm Hg (1 mm Hg=0.133 kPa) for 60 minutes], followed by intratracheal lipopolysaccharide 2 mg/kg (two-hit model). Ninety minutes after blood shedding, resuscitation phase II of 60 minutes began with hemostasis, return of all the blood initially shed, plus fluids. Observation phase III was 210 minutes. After phase III, blood gas analysis with carotid artery blood was performed. Lung tissue was sampled to measure values of wet-to-dry lung weight (W/D) ratio and pulmonary microvascular permeability. Immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR) were used to assess the expression of TGF-beta1 protein and mRNA, and the protein content of the smad2 was determined by Western blotting., Results: Compared with sham group, MAP was significantly lowered after 60 minutes in phase I, and lactic acid content was increased significantly, while partial pressure of oxygen in artery (PaO2), blood pH, HCO(-)3, arterial oxygen saturation (SaO2) and negative base excess (BE) showed a significant decrease in HS group. Concomitantly, values of pulmonary microvascular permeability and W/D ratio were significantly increased in HS group (all P<0.01). In sham group, weak TGF-beta1 staining was detected in the alveolar epithelial cells. However, intense positive immunostaining for TGF-beta1 was observed in alveolar epithelial cells, pulmonary interstitial inflammatory cell as well as macrophage cells of alveolar space of the HS group. Lung tissue in HS group demonstrated a marked increase in TGF-beta1 mRNA and smad2 protein expression in the lung tissue compared with those of sham group (all P<0.01)., Conclusion: The expression of TGF-beta1/smad2 signaling pathway may play an important role in regulation of pulmonary permeability and development of pulmonary edema in acute lung injury induced by uncontrolled hemorrhagic shock followed by lipopolysaccharide challenge.