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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. [ABSTRACT FROM AUTHOR]

Hemorrhagic shock/resuscitation involves overwhelming reactive oxygen species (ROS) that cause oxidative stress, inflammation, and subsequent tissue injury. We investigated the effects of the potent antioxidant carboxyfullerene (C 3 ) on acute liver injury during hemorrhage shock/resuscitation. C 3 infusion reduced the alanine aminotransferase (ALT) activity, methemoglobin content, malondialdehyde content, myeloperoxidase activity and expression levels of tumor necrosis factor -α and interleukin-6; it increased superoxide dismutase activity in the liver. The histologic injury score and apoptotic index were also markedly decreased after C 3 treatment compared with the vehicle group. Additionally, C 3 -treated rats showed a significant decrease in nuclear factor-κB DNA binding capacity, which was preceded by reduced phosphorylation of the nuclear factor κB (NF-κB) p65 subunit in the liver. C 3 nanoparticles ameliorate oxidative stress, the inflammatory response, and subsequent acute liver injury after hemorrhagic shock/resuscitation. These protective effects appear to be mediated through the inhibition of the nuclear factor-κB pathway. C 3 treatment may be a promising strategy to improve tissue injury in hemorrhagic shock/resuscitation. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to investigate the effect of hypertonic saline with 6% Dextran-70 (HSD) resuscitation on organ damage and the resuscitation efficiency of the combination of HSD and lactated ringers (LR) in a model of hemorrhage shock in dogs. Methods: Beagles were bled to hold their mean arterial pressure (MAP) at 50±5 mmHg for 1 h. After hemorrhage, beagles were divided into three groups (n = 7) to receive pre-hospital resuscitation for 1 h (R1): HSD (4 ml/kg), LR (40 ml/kg), and HSD+LR (a combination of 4 ml/kg HSD and 40 ml/kg LR). Next, LR was transfused into all groups as in-hospital resuscitation (R2). After two hours of observation (R3), autologous blood was transfused. Hemodynamic responses and systemic oxygenation were measured at predetermined phases. Three days after resuscitation, the animals were sacrificed and tissues including kidney, lung, liver and intestinal were obtained for pathological analysis. Results: Although the initial resuscitation with HSD was shown to be faster than LR with regard to an ascending MAP, the HSD group showed a similar hemodynamic performance compared to the LR group throughout the experiment. Compared with the LR group, the systemic oxygenation performance in the HSD group was similar but showed a lower venous-to-arterial CO2 gradient (Pv-aCO2) at R3 (p < 0.05). Additionally, the histology score of the kidneys, lungs and liver were significantly lower in the HSD group than in the LR group (p < 0.05). The HSD+LR group showed a superior hemodynamic response but higher extravascular lung water (EVLW) and lower arterial oxygen tension (PaO2) than the other groups (p < 0.05). The HSD+LR group showed a marginally improved systemic oxygenation performance and lower histology score than other groups. Conclusions: Resuscitation after hemorrhagic shock with a bolus of HSD showed a similar hemodynamic response compared with LR at ten times the volume of HSD, but HSD showed superior efficacy in organ protection. Our findings suggest that resuscitation with the combination of HSD and LR in the pre-hospital setting is an effective treatment. [ABSTRACT FROM AUTHOR]

Abstract: Nitric oxide (NO), an endothelial-derived relaxing factor, plays important roles in a variety of pathophysiological conditions such as hemorrhagic shock (HS). So far, the impact of NO administration in HS treatment has been controversial. Through literature review, we summarize here the biphasic effects of NO in early and late phases of HS. Evidence suggests that NO administration is beneficial in the early stage while detrimental in the late stage of HS. We further propose inhalation of NO as a novel therapeutic strategy for the treatment of HS in the early stage. [Copyright &y& Elsevier]

Background Uncontrolled hemorrhage (UH) remains the most common cause of death on the battlefield. This study examined the pathophysiological characteristics of UH in rats acutely exposed to high altitude. Material and methods Rats raised at sea level were randomly divided into two groups. Rats in the high-altitude group were exposed to hypobaric hypoxia in a hypobaric chamber (simulating 4000 m above sea level) for 2 d and then were performed a hemorrhagic shock protocol in the hypobaric chamber. Rats that underwent the same hemorrhage procedure at sea level were used as control. Anesthetized rats were bled to maintain their mean arterial pressure at 45 mmHg for 1 h. The distal quarter of the tail was amputated to allow free blood loss. After 1 h, the tail cut was ligated to induce hemostasis. mean arterial pressure, acid–base balance, blood loss, and survival were recorded. Rats were killed, and tissues were obtained for histological analysis. Results Rats in the high-altitude group suffered less uncontrolled blood loss, more severe acidosis (lower pH and base excess), and inferior tissue oxygen supply (lower oxygen saturation and higher arterial lactate concentration) during the hemorrhage periods compared with the control group. Survival rates were significantly lower in the high-altitude group than those in the control group ( P < 0.05), which was consistent with the results of pathological tissue injury. Conclusions In this rat model of hemorrhagic shock, acute high-altitude exposure resulted in decreased UH but more serious hemorrhagic shock injuries than that at sea level. [ABSTRACT FROM AUTHOR]