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Objectives: To evaluate the resuscitative efficacy and the effect on reperfusion injury of two site-specific PEGylated human serum albumins modified with linear or branched PEG20kDa, compared with saline, 8% human serum albumin and 25% human serum albumin, in a hemorrhagic shock model.Setting: Laboratory.Subjects: Male Wistar rats.Design: Prospective study.Interventions: Rats were bled to hemorrhagic hypovolemic shock and resuscitated with different resuscitation fluids.Measurements and Main Results: The mean arterial pressure and blood gas variables were measured. Hemorheology analysis was performed to evaluate the influence of resuscitation on RBCs and blood viscosity. The microvascular state was indirectly characterized in terms of monocyte chemotactic protein-1 and endothelial nitric oxide synthase that related to shear stress and vasodilation, respectively. The levels of inflammation-related factors and apoptosis-related proteins were used to evaluate the reperfusion injury in lungs. The results showed that PEGylated human serum albumin could improve the level of mean arterial pressure and blood gas variables more effectively at the end of resuscitation. poly(ethylene glycol) modification was able to increase the viscosity of human serum albumin to the level of effectively enhancing the expression of monocyte chemotactic protein-1 and endothelial nitric oxide synthase, which could promote microvascular perfusion. The hyperosmotic resuscitative agents including both 25% human serum albumin and PEGylated human serum albumins could greatly attenuate lung injury. No significant therapeutic advantages but some disadvantages were found for Y shaped poly(ethylene glycol) modification over linear poly(ethylene glycol) modification, such as causing the decrease of erythrocyte deformability.Conclusions: Linear high molecular weight site-specific PEGylated human serum albumin is recommended to be used as a hyperosmotic resuscitative agent. [ABSTRACT FROM AUTHOR]

The article presents a study which investigates the resuscitation with aged blood exacerbates liver injury in hemorrhagic anesthetized rat model. It states that the study was conducted at a research laboratory at the Hebrew University in Jerusalem, and used a prospective, controlled study and magnetic resonance imaging (MRI). Results show that stored blood showed reduction in the deformability of red blood cell (RBC).

The article details a study which determined the ideal target mean arterial pressure (MAP) and tolerance time for permissive hypotension. The study included rats with uncontrolled hemorrhagic shock. It found that a target resuscitation pressure of 50-60 millimeters of mercury (mmHg) is ideal for uncontrolled hemorrhagic shock.

The article presents a study which identifies whether increasing levels of O-linked β-N-acetylglucosamine (O-GlcNAc) could ameliorate post trauma-hemorrhage and resuscitation (TH-R). The study which adapted the volume-controlled hemorrhagic shock model, used male adult Sprague-Dawley rats wherein their organ injuries and inflammatory responses were examined. The result shows that O-GlcNAc increasing levels could ameliorate the 24-hr survival after undergoing a trauma hemorrhage.

The article presents a study which examines the role of fluid resuscitation in the renal oxygenation of rats with hemorrhagic shock. The authors utilized three phase hemorrhagic shock model to investigate the effects of fluid resuscitation on renal oxygenation. After one hour of shock phase, rats were randomized into four groups to receive either hypertonic saline or normal saline targeting a mean arterial pressure (MAP) of 40 or 80 mmHg. Results show that high MAP-directed fluid resuscitation (80 mmHg) does not increase renal microvascular oxygen pressure compared with fluid resuscitation targeted to 40 mmHg MAP. With regards to renal oxygenation, hypertonic saline is not superior to normal saline. Also, after blood transfusion the renal oxygenation decreases.

The article presents a study which examines the effect of billary tract external drainage on pathomorphism and cytokine expression of liver, lungs, and intestine in Sprague-Dawley rats with hemorrhagic shock. It reveals that billary tract external drainage has reduced the putrescence and exfoliation of intestinal vilii, denaturation and the infiltration of lung's inflammatory cells. It suggests that it decreases the messenger RNA expression of tumor necrosis factor and attenuate tissue injuries.

The article discusses an experimental study which investigated whether salutary effects of 17 beta-estradiol on cardiac function are mediated via Akt-dependent heme oxygenase (HO)-1 up-regulation. In this study, male rats underwent trauma-hemorrhage followed by fluid resuscitation. It discovered that 17 beta-estradiol prevented the trauma-hemorrhage-induced impairment in cardiac function. It concluded that the improvement in cardiac function occurred via Akt-dependent HO-1 up-regulation.

The article discusses the biological defect of Trauma-hemorrhagic shock (T/HS)-induced red blood cells (RBC) damage in blood circulation. Blood transfusion was performed in a rat's organ where trauma-sham shock (T/SS) or (T/HS) whole blood and RBC-depleted blood are examined. Tissue trapping, deformability and aggregation of RBC determine the blood flow passing through the heart. Findings show that T/HS stimulates a significant change in RBC functions that result to a decreased organ blood flow.

The article presents a study which investigates whether therapy with melatonin receptor agonist and hypnotic substance ramelteon may improve liver function, hepatic perfusion and hepatic integrity after hemorrhagic shock in art. It shows that an isolated activation of melatonin receptors may be sufficient for organ protection, independent from direct antioxidant effects. Furthermore, the hypnotic ramelteon play an interesting role in future sedation concepts for critical care patients.

The article presents a medical research to determine whether melatonin receptor activation can improve liver function and hepatic perfusion following a hemorrhagic shock. The study employed male rats that went through hemorrhagic shock and were resuscitated with Ringer's solution and shed blood. It was found that melatonin therapy improved liver function, hepatic perfusion, redox state and hepatic integrity after hemorrhagic shock.

The article investigates the impact of the interaction between mechanical ventilation and hemorrhagic shock-resuscitation on the release of inflammatory cytokine in rat models. The researchers determined whether hemorrhagic shock and resuscitation (HSR) and high lung stress during mechanical ventilation interact to augment lung and systemic inflammatory responses. They asserted that mechanical ventilation is an indispensable treatment of respiratory failure.

OBJECTIVE:: Hemorrhagic shock and resuscitation trigger a global ischemia/reperfusion phenomenon, in which various inflammatory processes critically contribute to the ensuing tissue damage. Adenosine is an endogenous nucleoside that is released during shock. Activation of adenosine A2A receptors can broadly inactivate inflammatory cascades. The current study was designed to evaluate the effect of A2A receptor activation on organ injury and inflammation in the setting of global ischemia/reperfusion elicited by trauma/hemorrhagic shock and resuscitation. DESIGN:: Prospective animal study with concurrent control. SETTING:: Small animal laboratory. SUBJECTS:: Adult male Sprague-Dawley rats. INTERVENTIONS:: The rats were subjected to a laparotomy (trauma) and 90 mins of hemorrhagic shock or trauma/sham shock. The selective A2A receptor agonist CGS-21680 (2-p-(2-carboxyethyl) phenethylamino-5′-N-ethyl-carboxamidoadenosine; 0.5 mg/kg) or its vehicle was injected 30 mins before shock or immediately after resuscitation. At 3 hrs following resuscitation, animals were killed and tissue was harvested for analysis. Lung permeability and pulmonary myeloperoxidase levels were used to quantitate lung injury. Intestinal injury was determined by histologic analysis of terminal ileum. Red blood cell deformability was measured by a laser-assisted ektacytometer. In this assay, a decrease in the elongation index is a marker of decreased red blood cell deformability. MEASUREMENTS AND MAIN RESULTS:: Pretreatment with CGS-21680 protected the lung but not the gut against shock-induced injury and prevented the shock-induced decrease in red blood cell deformability. Posttreatment with CGS-21680 ameliorated shock-induced lung injury but failed to prevent gut injury and preserve red blood cell deformability. CONCLUSION:: A2A receptor agonists may represent a novel therapeutic approach in preventing organ injury following trauma/hemorrhagic shock. [ABSTRACT FROM AUTHOR]

The author comments on the study by Shellington et al which investigated the effectiveness of polynitroxylated pegylated hemoglobin (PNP-Hb) for fluid resuscitation of traumatic patients with hemorrhagic shock in rats. He stresses that the strength of the study includes the use of the combined in vitro and in vivo approach, experimental technique in vivo, the experimental protocol and the use of relevant control compounds. He also cites the weak points of the study including the lack of insight into the neuroprotective mechanisms of PNP-Hb.

The author discusses a laboratory study on resuscitation from uncontrolled hemorrhagic shock in rats published within the issue. The study demonstrated that fluid administration can be harmful during early resuscitation. The author cites the questions raised by the study findings. He also ponders on the clinical implications of the study findings.