Search

Background: Oxidative stress induced by hemorrhagic shock (HS) is known to initiate a systemic inflammatory response, which leads to subsequent acute lung injury. This study is aimed to assess the efficacy of exendin-4 (Ex-4) in attenuating lung injury in a rat model of HS and resuscitation (HS/R)., Methods: HS was induced in sodium pentobarbital-anesthetized adult male Wistar rats by withdrawing blood to maintain a mean arterial pressure of 30-35 mm Hg for 50 min. Then, the animals received Ex-4 (5 μg/kg) or vehicle (saline) intravenously and were resuscitated with a volume of normal saline 1.5 times that of the shed blood volume. Mean arterial pressure was measured throughout the experiment, and acid-base status, oxidative stress, inflammation, and lung injury were evaluated at 2 h after resuscitation., Results: Ex-4 infusion reduced the methemoglobin content, the malondialdehyde content, the myeloperoxidase activity, and the expression of tumor necrosis factor-α and interleukin-6 in the lungs. The histologic injury was also markedly decreased in the Ex-4 group compared with the vehicle group., Conclusions: Ex-4 ameliorates the oxidative stress, inflammatory response, and subsequent acute lung injury occurring after HS/R. Although future studies are required to elucidate the underlying mechanism, our results indicate that Ex-4 infusion may be a promising strategy for improving lung injury in the treatment of HS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To compare the efficacy of hypotensive resuscitation with hypertonic saline dextran 70 (HSD) and lactated Ringer (LR) solutions in a rat model of hemorrhagic shock at a simulated altitude of 4,000 m., Methods: Anesthetized rats were bled to maintain their mean arterial pressure (MAP) at 45 mm Hg for 1 h. The distal quarter of the tail was then amputated to allow free blood loss; rats were simultaneously resuscitated with 4 mL kg HSD (HSD group, n = 10) or 4 mL kg LR (LR group, n = 10), followed by hypotensive resuscitation with LR to maintain MAP at 55 to 60 mm Hg for 1 h. A control group received no resuscitation (n = 10). Afterward, the cut end of the tail was ligated. The MAP, acid-base balance, blood loss, volume of fluid infused, and survival were recorded., Results: Compared with controls, HSD resuscitation improved MAP (without increasing uncontrolled blood loss), increased arterial pH and oxygen saturation (SaO2), decreased arterial lactate concentration at the end of resuscitation, and resulted in higher survival rate (P < 0.05). Hypotensive resuscitation with LR also maintained higher MAP, pH, and SaO2 than the control group, but was associated with increased blood loss and inferior survival (P > 0.05)., Conclusions: For hemorrhagic shock at simulated high altitude, resuscitation of rats with a bolus of HSD was associated with reduced blood loss and serum lactate concentration, and superior SaO2, hemoglobin concentration and survival rate, compared with LR solution.

Background: The optimal oxygen administration strategy during resuscitation from hemorrhagic shock (HS) is still controversial. Improving oxygenation and mitigating oxidative stress simultaneously seem to be contradictory goals. To maximize oxygen delivery while minimizing oxidative damage, the authors proposed the notion of gradually increased oxygen administration (GIOA), which entails making the arterial blood hypoxemic early in resuscitation and subsequently gradually increasing to hyperoxic, and compared its effects with normoxic resuscitation, hyperoxic resuscitation, and hypoxemic resuscitation in severe HS., Methods: Rats were subjected to HS, and on resuscitation, the rats were randomly assigned to four groups (n = 8): the normoxic, the hyperoxic, the hypoxemic, and the GIOA groups. Rats were observed for an additional 1 h. Hemodynamics, acid-base status, oxygenation, and oxidative injury were observed and evaluated., Results: Central venous oxygen saturation promptly recovered only in the hyperoxic and the GIOA groups, and the liver tissue partial pressure of oxygen was highest in the GIOA group after resuscitation. Oxidative stress in GIOA group was significantly reduced compared with the hyperoxic group as indicated by the reduced malondialdehyde content, increased catalase activity, and the lower histologic injury scores in the liver. In addition, the tumor necrosis factor-α and interleukin-6 expressions in the liver were markedly decreased in the GIOA group than in the hyperoxic and normoxic groups as shown by the immunohistochemical staining., Conclusions: GIOA improved systemic/tissue oxygenation and mitigated oxidative stress simultaneously after resuscitation from severe HS. GIOA may be a promising strategy to improve resuscitation from HS and deserves further investigation.

Background: We aimed to evaluate the effects of resuscitation with different ratios of fresh frozen plasma (FFP) to red blood cells (RBCs) on pulmonary inflammatory injury and to illuminate the beneficial effects of FFP on lung protection compared with lactated ringers (LR) using a rat model of hemorrhagic shock., Methods: Rats underwent pressure-controlled hemorrhage for 60 minutes and were then transfused with LR for initial resuscitation. Thereafter, the rats were transfused with varying ratios of FFP:RBC (1:4, 1:2, 1:1, and 2:1) or LR:RBC (1:1) to hold their mean arterial pressure (MAP) at 100 ± 3 mm Hg for 30 minutes. After 4 hours of observation, lung tissue was harvested to determine the wet/dry weight, myeloperoxidase levels, tumor necrosis factor α levels, macrophage inflammatory protein 2 (MIP-2) levels, inducible nitric oxide synthase activity, and the nuclear factor κB p65 DNA-binding activity., Results: With an increase in the FFP:RBC ratio, the volume of required RBC to maintain the target MAP decreased. The MAP value in each group was not significantly different during the whole experiment period. The values of the wet/dry weights and MIP-2 were significantly lower in the FFP:RBC = 1:1 group than the other groups (P < .05). All parameters detected above were predominantly lower in the FFP:RBC = 1:1 group than the FFP:RBC = 1:2 group and the LR:RBC = 1:1 group (P < .05). In addition, all parameter values were lower in the FFP:RBC = 1:1 group than in the FFP:RBC = 2:1 group, but only the wet/dry weight, myeloperoxidase, and MIP-2 values were significantly different (P < .05)., Conclusions: Resuscitation with a 1:1 ratio of FFP to RBC results in decreased lung inflammation. Compared with LR, FFP could further mitigate lung inflammatory injury., (Copyright © 2015. Published by Elsevier Inc.)

Background: Hemorrhagic shock is associated with severe rheological abnormalities. We hypothesized that in the setting of hemorrhagic shock, resuscitation can alter hemorheological characteristics dramatically, and different fluids cause different effects. The aim of this study was to investigate whether the type of fluid administered has an impact on hemorheological characteristics at the early stage of resuscitation in a rodent model of hemorrhagic shock., Methods: Animals were randomized into five groups: (1) sham hemorrhage (SHAM); (2) shock and sham resuscitation (SHOCK); (3) shock and resuscitation with normal saline 32 ml/kg (NS); (4) shock and resuscitation with 7.5% hypertonic saline 4 ml/kg (HS); (5) shock and resuscitation with 7.5% hypertonic saline/6% Dextran 70 4 ml/kg (HSD). Hemorheological characteristics were measured at 60 min after resuscitation., Results: Results showed that NS resuscitation deteriorated red blood cell (RBC) deformability compared with the SHOCK group. The HS group showed improved RBC deformability compared with the NS group, although the differences were not statistically significant. There were significant improvements of RBC deformability at all shear rates in the HSD group compared with the NS group. Whole blood and plasma viscosities decreased significantly in the SHOCK group compared with the SHAM group. At shear rates of 60 and 150 s(-1), the NS group decreased whole blood viscosity compared with the SHOCK group. The HSD group showed elevated plasma viscosity compared with the SHOCK, NS and HS groups., Conclusion: These results suggested that at the early stage of hemorrhagic shock resuscitation, hypertonic-hyperoncotic resuscitation could improve RBC deformability compared with isotonic crystalloid resuscitation. Dextran 70 could elevate plasma viscosity to nearly baseline level. These effects of hypertonic-hyperoncotic resuscitation could be beneficial to maintain microcirculation.

Oxidative stress induced by hemorrhagic shock (HS) initiates a systemic inflammatory response, which leads to subsequent kidney injury. This study assessed the efficacy of c-type natriuretic peptide (CNP) in attenuating kidney injury in a rat model of hemorrhagic shock and resuscitation (HS/R). Sodium pentobarbital-anesthetized adult male Wistar rats underwent HS induced by the withdrawal of blood to a mean arterial pressure of 30-35 mmHg for 50 min. Then, the animals received CNP (25 μg/kg) or vehicle (saline) intravenously, followed byresuscitation with 1.5 times the shed blood volume in the form of normal saline. Mean arterial pressure was measured throughout the experiment, and acid-base status, oxidative stress, inflammation, tissue injury and kidney function were evaluated after resuscitation. CNP infusion reduced the malondialdehyde content, lowered the myeloperoxidase activity and decreased the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the kidney. The histologic injury score and the plasma creatinine concentration were also significantly decreased after CNP treatment compared to the vehicle group. CNP treatment ameliorates oxidative stress, the inflammatory response, and consequently acute kidney injury after HS/R. Thus, CNP may represent a promising strategy to improve resuscitation for the treatment of HS and deserves further investigation. [ABSTRACT FROM AUTHOR]