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Aim: Severely injured patients experience substantial immunological stress upon traumatic insult. Next to the direct local tissue injury also other organs, which are not directly injured such as liver and lung, are frequently affected by a so-called remote organ damage (ROD) after trauma. Thus, we studied the inflammatory response of lung and liver either after isolated femur fracture as example for ROD, or after multiple trauma in a porcine polytrauma model., Methods: Twenty-four male pigs (Sus scrofa) underwent either isolated standardized femoral fracture (monotrauma, MT, n = 12) or polytrauma (PT, n = 12). PT consisted of a femur fracture, lung contusion, liver laceration, hemorrhagic shock, subsequent resuscitation and surgical fracture fixation. Six animals served as controls (sham). After 72 h inflammatory changes were determined by analyses of the interleukin (IL)-6 gene expression and tissue infiltration of polymorphonuclear leukocyte (PMN, myeloperoxidase staining). ROD in MT, and lung as well as liver damage in PT were assessed histologically by hematoxylin-eosin staining. Expression of phosphorylated p65 NF-κB was evaluated by immunohistology., Results: IL-6 increased in lungs and liver in both groups MT and PT, respectively, compared to sham. Similarly, PMN infiltration of the lungs and liver increased significantly after both MT and PT compared to sham. Histological evaluation demonstrated tissue damage notably in lungs after MT, while tissue damage after PT was found in both lung and liver after PT. p65 NF-κB tended to an increase upon MT, and was significantly enhanced after PT in both tissues., Conclusion: Our data indicate that remote organ damage after MT notably in lungs was associated with an enhanced inflammatory response. Severe polytrauma substantially intensifies this response and organ damage in the underlying model.

Due to their high prevalence, blunt chest trauma (TxT) and hemorrhagic shock have a significant influence on the outcomes of trauma patients, causing severe modulations of the immune system and high mortality rates. Alcohol consumption in trauma patients has a high clinical impact. Studies investigating the timing of alcohol intoxication prior to trauma are limited, although there are two typical scenarios regarding alcohol consumption: Acute ('drink and drive scenario') and sub‑acute ('evening binge drinking'). Therefore, the present study investigated the influence of either an acute or sub‑acute alcohol‑drinking scenario in an in vivo model of TxT and hemorrhagic shock, focusing on liver inflammation and outcomes. At 12 h (sub‑acute) or 2 h (acute) before the experiment, female Lewis rats received a single oral dose of alcohol (ethanol, EtOH) or saline (NaCl, ctrl), followed by TxT, hemorrhagic shock (35±3 mm Hg) and resuscitation (H/R). The animals were either sacrificed 2 h later or their survival was determined for 72 h. The results revealed that EtOH induced significant fatty changes in the liver. TxT + H/R‑induced increases in the gene expression of interleukin (IL)‑6 and intercellular adhesion molecule‑1 and the protein expression of tumor necrosis factor (TNF)‑α and IL‑1β were significantly reduced in both EtOH groups compared with those in the corresponding TxT + H/R ctrl groups. The local presence of IL‑10‑expressing cells in the liver was significantly increased following TxT + H/R in all groups, although the sub‑acute EtOH TxT + H/R group had a significantly higher proportion of IL‑10‑positive cells compared with all other groups. Stimulating peripheral whole blood with lipopolysaccharide led to significantly lower levels of TNF‑α release in the sub‑acute EtOH group compared with the levels in all other groups. Significant TxT + H/R‑induced increases in liver transaminases and liver damage were most prominent in the sub‑acute EtOH group. The TxT + H/R EtOH group exhibited the lowest levels of glucose. There were no significant differences in mortality rate among the TxT + H/R groups. The data obtained indicates that the severity of liver damage following TxT + H/R may depend on the timing of alcohol consumption and severity of trauma, but also on the balance between pro‑ and anti‑inflammatory responses.

Aim: To evaluate protective immunosuppressive dose and time-dependent effects of ethanol in an in vitro model of acute inflammation in human Chang liver cells., Method: The study was performed in 2016 and 2017 in the research laboratory of the Department of Trauma, Hand and Reconstructive Surgery, the University Hospital of the Goethe-University Frankfurt. Chang liver cells were stimulated with either interleukin (IL)-1β or IL-6 and subsequently treated with low-dose ethanol (85 mmol/L) or high-dose ethanol (170 mmol/L) for one hour (acute exposure) or 72 hours (subacute exposure). IL-6 and IL-1β release were determined by enzyme-linked immunosorbent assay. Neutrophil adhesion to Chang liver monolayers, production of reactive oxygen species, and apoptosis or necrosis were analyzed., Results: Contrary to high-dose ethanol, acute low-dose ethanol exposure significantly reduced IL-1β-induced IL-6 and IL-6-induced IL-1β release (P<0.05). Subacute ethanol exposure did not change proinflammatory cytokine release. Acute low-dose ethanol exposure significantly decreased inflammation-induced formation of reactive oxygen species (P<0.05) and significantly improved cell survival (P<0.05). Neither acute nor subacute high-dose ethanol exposure significantly changed inflammation-induced changes in reactive oxygen species or survival. Acute and subacute ethanol exposure, independently of the dose, significantly decreased neutrophil adhesion to inflamed Chang liver cells (P<0.05)., Conclusion: Acute treatment of inflamed Chang liver cells with ethanol showed its immunosuppressive potential. However, the observed effects were limited to low-dose setting, indicating the relevance of ethanol dose in the modulation of inflammatory cell response.

Background: The treatment of patients with multiple trauma including blunt chest/thoracic trauma (TxT) and hemorrhagic shock (H) is still challenging. Numerous studies show detrimental consequences of TxT and HS resulting in strong inflammatory changes, organ injury and mortality. Additionally, the reperfusion (R) phase plays a key role in triggering inflammation and worsening outcome. Ethyl pyruvate (EP), a stable lipophilic ester, has anti-inflammatory properties. Here, the influence of EP on the inflammatory reaction and liver injury in a double hit model of TxT and H/R in rats was explored., Methods: Female Lewis rats were subjected to TxT followed by hemorrhage/H (60 min, 35±3 mm Hg) and resuscitation/R (TxT+H/R). Reperfusion was performed by either Ringer`s lactated solution (RL) alone or RL supplemented with EP (50 mg/kg). Sham animals underwent all surgical procedures without TxT+H/R. After 2h, blood and liver tissue were collected for analyses, and survival was assessed after 24h., Results: Resuscitation with EP significantly improved haemoglobin levels and base excess recovery compared with controls after TxT+H/R, respectively (p<0.05). TxT+H/R-induced significant increase in alanine aminotransferase levels and liver injury were attenuated by EP compared with controls (p<0.05). Local inflammation as shown by increased gene expression of IL-6 and ICAM-1, enhanced ICAM-1 and HMGB1 protein expression and infiltration of the liver with neutrophils were also significantly attenuated by EP compared with controls after TxT+H/R (p<0.05). EP significantly reduced TxT+H/R-induced p65 activation in liver tissue. Survival rates improved by EP from 50% to 70% after TxT+H/R., Conclusions: These data support the concept that the pronounced local pro-inflammatory response in the liver after blunt chest trauma and hemorrhagic shock is associated with NF-κB. In particular, the beneficial anti-inflammatory effects of ethyl pyruvate seem to be regulated by the HMGB1/NF-κB axis in the liver, thereby, restraining inflammatory responses and liver injury after double hit trauma in the rat.

Background and Purpose: Chronic ethanol abuse and haemorrhagic shock are major causes of global mortality and, separately, induce profound hepato- and immune-toxic effects via activation of NF-κB. Here, we assessed the effects of chronic ethanol intake upon the pathophysiological derangements after haemorrhagic shock with subsequent resuscitation (H/R), with particular attention to the contribution of NF-κB., Experimental Approach: Transgenic NF-κB(EGFP) mice, expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-κB cis-elements were fed a Lieber-DeCarli diet containing ethanol (EtOH-diet) or an isocaloric control diet for 4 weeks and were then pairwise subjected to H/R. Liver tissues and peripheral blood were sampled at 2 or 24 h after H/R. Cytokines in blood and tissue and leukocyte activation (as CD11b expression) were measured, along with EGFP as a marker of NF-κB activation., Key Results: The EtOH-diet increased mortality at 24 h after H/R and elevated liver injury, associated with an up-regulation of NF-κB-dependent genes and IL-6 release; it also increased production of NF-κB-driven intercellular adhesion molecule 1 (ICAM-1) and EGFP in liver tissue. At 2h after the H/R procedure in ethanol-fed mice we observed the highest proportion of NF-κB activated non-parenchymal cells and an NF-κB-dependent increase in polymorphonuclear leukocyte CD11b expression., Conclusions and Implications: The EtOH-diet exacerbated liver injury after H/R, accompanying an overwhelming hepatic and systemic immune response. Our findings contribute to evidence implicating NF-κB as a key player in the orchestration of the immune response in haemorrhagic shock patients with a history of chronic ethanol abuse., (© 2013 The British Pharmacological Society.)

Background: The incidence of pulmonary failure in trauma patients is considered to be influenced by several factors such as liver injury. We intended to assess the association of various potential predictors of pulmonary failure following thoracic trauma and liver injury., Methods: Records of 12,585 trauma patients documented in the TraumaRegister DGU® of the German Trauma Society were analyzed regarding the potential impact of concomitant liver injury on the incidence of pulmonary failure using uni- and multivariate analyses. Pulmonary failure was defined as pulmonary failure of ≥ 3 SOFA-score points for at least two days. Patients were subdivided according to their injury pattern into four groups: group 1: AIS thorax < 3; AIS liver < 3; group 2: AIS thorax ≥ 3; AIS liver < 3; group 3: AIS thorax < 3; AIS liver ≥ 3 and group 4: AIS thorax ≥ 3; AIS liver ≥ 3., Results: Overall, 2643 (21%) developed pulmonary failure, 12% (n= 642) in group 1, 26% (n= 697) in group 2, 16% (n= 30) in group 3, and 36% (n= 188) in group 4. Factors independently associated with pulmonary failure included relevant lung injury, pre-existing medical conditions (PMC), sex, transfusion of more than 10 units of packed red blood cells (PRBC), Glasgow Coma Scale (GCS) ≤ 8, and the ISS. However, liver injury was not associated with an increased risk of pulmonary failure following severe trauma in our setting., Conclusions: Specific factors, but not liver injury, were associated with an increased risk of pulmonary failure following trauma. Trauma surgeons should be aware of these factors for optimized intensive care treatment.

The leading causes of death in people aged 1 to 44 years are unintentional injuries with associated hemorrhagic shock. Hemorrhagic shock followed by resuscitation (H/R) activates the nuclear factor κB (NF-κB) pathway. To further address the association between liver damage and NF-κB activation, we analyzed the H/R-induced activation of NF-κB using cis-NF-κB reporter gene mice. In these mice, the expression of green fluorescent protein (GFP) is linked to the activation of NF-κB, and therefore tracing of GFP colocalizes NF-κB activation. Mice were hemorrhaged to a mean arterial blood pressure of 30mmHg for 90 min, followed by resuscitation. Six, 14, or 24 h after resuscitation, mice were killed. Compared with sham-operated mice, H/R led to a profound hepatic and cellular damage as measured by aspartate aminotransferase, creatine kinase, and lactate dehydrogenase levels, which was accompanied by an elevation in interleukin 6 levels and hepatic leukocyte infiltration. Interleukin 10 levels in plasma were elevated 6 h after H/R. Using serial liver sections, we found an association between necrotic areas, oxidative stress, and enhanced GFP-positive cells. Furthermore, enhanced GFP-positive cells surrounded areas of necrotic liver tissue, predominantly in a penumbra-like-shape pericentrally. These results elucidate spatial relationship between oxidative stress, liver necrosis, and NF-κB activation, using an in vivo approach and therefore might help to further analyze mechanisms of NF-κB activation after resuscitated blood loss.

Purpose: Oxidative stress and inflammation contribute to hepatic injury after hemorrhage/resuscitation (H/R). Natural plant polyphenols, i.e., green tea extract (GTE) possess high anti-oxidant and anti-inflammatory activities in various models of acute inflammation. However, possible protective effects and feasible mechanisms by which plant polyphenols modulate pro-inflammatory, apoptotic, and oxidant signaling after H/R in the liver remain unknown. Therefore, we investigated the effects of GTE and its impact on the activation of NF-kappaB in the pathogenesis of hepatic injury induced by H/R., Methods: Twenty-four female LEWIS rats (180-250 g) were fed a standard chow (ctrl) or a diet containing 0.1% polyphenolic extracts (GTE) from Camellia sinensis starting 5 days before H/R. Rats were hemorrhaged to a mean arterial pressure of 30 ± 2 mmHg for 60 min and resuscitated (H/R and GTE H/R groups). Control groups (sham, ctrl, and GTE) underwent surgical procedures without H/R. Two hours after resuscitation, tissues were harvested., Results: Plasma alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) increased 3.5-fold and fourfold, respectively, in vehicle-treated rats as compared to GTE-fed rats. Histopathological analysis revealed significantly decreased hepatic necrosis and apoptosis in GTE-fed rats after H/R. Real-time PCR showed that GTE diminished gene expression of pro-apoptotic caspase-8 and Bax, while anti-apoptotic Bcl-2 was increased after H/R. Hepatic oxidative (4-hydroxynonenal) and nitrosative (3-nitrotyrosine) stress as well as systemic IL-6 level and hepatic IL-6 mRNA were markedly reduced in GTE-fed rats compared with controls after H/R. Plant polyphenols also decreased the activation of both JNK and NFκB., Conclusions: Taken together, GTE application blunts hepatic damage, apoptotic, oxidative, and pro-inflammatory changes after H/R. These results underline the important roles of JNK and NF-kappaB in inflammatory processes after H/R and the beneficial impact of plant polyphenols in preventing their activation.

Acute ethanol intoxication increases the production of reactive oxygen species (ROS). Hemorrhagic shock with subsequent resuscitation (H/R) also induces ROS resulting in cellular and hepatic damage in vivo. We examined the role of acute ethanol intoxication upon oxidative stress and subsequent hepatic cell death after H/R. 14 h before H/R, rats were gavaged with single dose of ethanol or saline (5 g/kg, EtOH and ctrl; H/R&#95;EtOH or H/R&#95;ctrl, resp.). Then, rats were hemorrhaged to a mean arterial blood pressure of 30 ± 2 mmHg for 60 min and resuscitated. Two control groups underwent surgical procedures without H/R (sham&#95;ctrl and sham&#95;EtOH, resp.). Liver tissues were harvested at 2, 24, and 72 h after resuscitation. EtOH-gavage induced histological picture of acute fatty liver. Hepatic oxidative (4-hydroxynonenal, 4-HNE) and nitrosative (3-nitrotyrosine, 3-NT) stress were significantly reduced in EtOH-gavaged rats compared to controls after H/R. Proapoptotic caspase-8 and Bax expressions were markedly diminished in EtOH-gavaged animals compared with controls 2 h after resuscitation. EtOH-gavage increased antiapoptotic Bcl-2 gene expression compared with controls 2 h after resuscitation. iNOS protein expression increased following H/R but was attenuated in EtOH-gavaged animals after H/R. Taken together, the data suggest that acute EtOH-gavage may attenuate H/R-induced oxidative stress thereby reducing cellular injury in rat liver.

Objectives: Fatty acid-binding proteins (FABPs) have relatively high tissue concentrations and low plasma concentrations and are released into the circulation following organ injury. We explored the utility of intestinal-(I)-FABP and liver-(L)-FABP for the diagnosis of abdominal injury in patients with multiple trauma., Methods: This prospective study included 102 trauma patients and 30 healthy volunteers. Plasma I-FABP and L-FABP levels were measured in the emergency department (ED) by enzyme-linked immunosorbent assay (ELISA). Forty-one patients suffered from serious or severe abdominal trauma (Abbreviated Injury Score [AIS] code "ai" for abdominal injury, AISai > or = 3) and nine were moderately abdominally injured (AISai < 3). Fifty-two had no abdominal injury., Results: Median I-FABP and L-FABP levels in the AISai > or = 3 group (516 pg/mL and 135 ng/mL, respectively) were significantly higher compared to the AISai < 3 group (154 pg/mL and 13 ng/mL, respectively) or those without abdominal injury (207 pg/mL and 21 ng/mL, respectively) or normal controls (108 pg/mL and 13 ng/mL, respectively). The cutoff to distinguish the ai > or = 3 is 359 pg/mL for I-FABP and 54 ng/mL for L-FABP, with 93% specificity and 75% sensitivity for I-FABP and 93% and 82% for L-FABP, respectively., Conclusions: High I-FABP and L-FABP levels correlate with relevant severity of abdominal tissue damage in patients with multiple trauma. I-FABP and L-FABP could be useful as markers for the early detection of significant abdominal injury in acute multiple trauma and identify patients who require rapid intervention., (2010 by the Society for Academic Emergency Medicine)

Statins are established in the prevention and therapy of chronic cardiovascular diseases because of inhibition of HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A), thus lowering blood cholesterol levels. However, their cholesterol-independent effects include regulation of Rho/Rho-kinases (ROCK) and eNOS, proteins centrally involved in various models of acute inflammation. Therefore, we tested the hypothesis that simvastatin confers protection after rat hemorrhage/resuscitation (H/R) and wanted to elucidate the mechanisms involved. Fifty-two female Lewis rats (180-250 g) were pretreated with simvastatin 5 mg/kg per day or vehicle for 6 days (i.p.). Then, rats were hemorrhaged to a mean arterial pressure of 30 +/- 2 mmHg for 60 min and resuscitated. Control group underwent surgical procedures without H/R. Two hours after resuscitation, tissues were harvested. Mortality was assessed 72 h after H/R. Simvastatin pretreatment increased survival after H/R from 20% to 80%. Serum alanine aminotransferase after H/R increased 2.2-fold in vehicle as compared with simvastatin-treated rats. Histopathological analysis revealed decreased hepatic necrosis in simvastatin-treated rats after H/R. Hepatic oxidative (4-hydroxynonenal) and nitrosative (3-nitrotyrosine) stress, inflammatory markers (serum IL-6 and hepatic infiltration with polymorphonuclear leukocytes), and actin cytoskeleton rearrangements were decreased after simvastatin pretreatment compared with vehicle-treated rats after H/R. Simvastatin increased eNOS and heme oxygenase 1 expression and eNOS activation. Expression of Rho/Rho-kinase and myosin phosphatase targeting subunit, Thr-MYPT1, a marker for Rho-kinase activity, decreased after simvastatin treatment compared with vehicle-treated rats after H/R. Simvastatin pretreatment exerts beneficial effects in this model of acute inflammation by supporting protective mechanisms that are important for hepatic microcirculation after H/R.

Inhibition of c-Jun N-terminal kinase (JNK) by a cell-penetrating, protease-resistant JNK peptide (D-JNKI-1) before hemorrhage and resuscitation (H/R) ameliorated the H/R-induced hepatic injury and blunted the proinflammatory changes. Here we tested the hypothesis if JNK inhibition at a later time point-after hemorrhagic shock but before the onset of resuscitation-in a rat model of H/R also confers protection. Twenty-four male Sprague-Dawley rats (250 - 350 g) were randomly divided into 4 groups: 2 groups of shock animals were hemorrhaged to a MAP of 32 to 37 mmHg for 60 min and randomly received either D-JNKI-1 (11 mg/kg i.p.) or sterile saline as vehicle immediately before the onset of resuscitation. Two groups of sham-operated animals underwent surgical procedures without H/R and were either D-JNKI-1 or vehicle treated. Rats were killed 2 h later. Serum activity of alanine aminotransferase and serum lactate dehydrogenase after H/R increased 3.5-fold in vehicle-treated rats as compared with D-JNKI-1-treated rats. Histopathological analysis revealed that hepatic necrosis and apoptosis (hematoxylin-eosin, TUNEL, and M30, respectively) were significantly inhibited in D-JNKI-1-treated rats after H/R. Hepatic oxidative (4-hydroxynonenal) and nitrosative (3-nitrotyrosine) stress as well as markers of inflammation (hepatic and serum IL-6 levels and hepatic infiltration with polymorphonuclear leukocytes) were also reduced in D-JNKI-1-treated rats. LPS-stimulated TNF-alpha release from whole blood from hemorrhaged and resuscitated animals was higher in vehicle-treated rats as compared with D-JNKI-1-treated rats. c-Jun N-terminal kinase inhibition after hemorrhage before resuscitation resulted in a reduced activation of c-Jun. Taken together, these results indicate that D-JNKI-1 application after hemorrhagic shock before resuscitation blunts hepatic damage and proinflammatory changes during resuscitation. Hence, JNK inhibition is even protective when initiated after blood loss before resuscitation. These experimental results indicate that the JNK pathway may be a possible treatment option for the harmful consequences of H/R.

Hemorrhage and resuscitation (H/R) leads to phosphorylation of mitogen-activated stress kinases, an event that is associated with organ damage. Recently, a specific, cell-penetrating, protease-resistant inhibitory peptide of the mitogen-activated protein kinase c-JUN N-terminal kinase (JNK) was developed (D-JNKI-1). Here, using this peptide, we tested if inhibition of JNK protects against organ damage after H/R. Male Sprague-Dawley rats were treated with D-JNKI-1 (11 mg/kg, i.p.) or vehicle. Thirty minutes later, rats were hemorrhaged for 1 h to a MAP of 30 to 35 mmHg and then resuscitated with 60% of the shed blood and twice the shed blood volume as Ringer lactate. Tissues were harvested 2 h later. ANOVA with Tukey post hoc analysis or Kruskal-Wallis ANOVA on ranks, P < 0.05, was considered significant. c-JUN N-terminal kinase inhibition decreased serum alanine aminotransferase activity as a marker of liver injury by 70%, serum creatine kinase activity by 67%, and serum lactate dehydrogenase activity by 60% as compared with vehicle treatment. The histological tissue damage observed was blunted after D-JNKI-1 pretreatment both for necrotic and apoptotic cell death. Hepatic leukocyte infiltration and serum IL-6 levels were largely diminished after D-JNKI-1 pretreatment. The extent of oxidative stress as evaluated by immunohistochemical detection of 4-hydroxynonenal was largely abrogated after JNK inhibition. After JNK inhibition, activation of cJUN after H/R was also reduced. Hemorrhage and resuscitation induces a systemic inflammatory response and leads to end-organ damage. These changes are mediated, at least in part, by JNK. Therefore, JNK inhibition deserves further evaluation as a potential treatment option in patients after resuscitated blood loss.

Background: Dichloromethylenebisphosphonate (MDP) and gadolinium chloride (GdCl(3)) are substances frequently used for experimental depletion of Kupffer Cells (KC) in models of endotoxin shock. The aim was to determine whether depletion of KC through pretreatment with GdCl(3) or MDP alters the hepatic microcirculation during lipopolysaccharide (LPS)-induced shock in rats and to test if there are substance-specific differences., Methods: Rats received either MDP or GdCl(3) or saline prior to induction of LPS shock. Hepatic microcirculation was evaluated by intravital microscopy (sinusoidal diameter, sinusoidal bloodflow, leukocyte adhesion), and the gene expression in the hepatic non-parenchymal cell fraction was determined by RT-PCR., Results: GdCl(3) pretreatment prevented sinusoidal narrowing but did not restore sinusoidal blood flow and did not normalize leukocyte-endothelial interaction time after LPS. In contrast, MDP pretreatment improved hepatic microcirculation consistently for all parameters measured compared to GdCl(3) pretreated animals. In the non-parenchymal cell fraction, eNOS gene expression was preserved and gene expression of TNF-alpha was blocked after MDP but not after GdCl(3) application prior to LPS shock., Conclusions: The results show that GdCl(3) and MDP cannot be used equivalently for experimental KC depletion in the condition of LPS-induced shock. These findings should be taken into consideration in studies that evaluate the role of Kupffer cells in models of endotoxin-induced shock.

Hepatic microcirculatory disorders such as narrowing of sinusoids after hemorrhagic shock play a major role in the pathogenesis of organ failure. It is known that the balance of vasoactive mediators such as endothelin and nitric oxide (NO) regulate microvascular perfusion, including the diameter of hepatic sinusoids. The present study was designed to evaluate the role of exogenous substitution of NO by S-nitroso-albumin (S-NO-HSA) in the prevention of pathophysiological alterations of hepatic microcirculation. Anesthetized Sprague-Dawley rats were instrumented for invasive hemodynamic monitoring. Hemorrhagic shock was induced by bleeding to a mean arterial pressure (MAP) of 40 mmHg and was maintained for 60 min. Thereafter, the animals were resuscitated with shed blood and Ringer's solution. During the first hour of resuscitation, S-NO-HSA or pure HSA was infused continuously (10 micromol/kg/h) and hepatic microcirculation was detected by intravital epifluorescence microscopy either 5 or 24 h after the insult. Results were compared with a sham-treated group (n = 6-8 per group). Shock-induced microcirculatory narrowing of sinusoids was significantly reduced in the S-NO-HSA group compared with the HSA group both at 5 and 24 h (HSA: 9.3 +/- 0.2 microm; S-NO-HSA: 12.1 +/- 0.2 microm, P < 0.05). Sinusoidal perfusion was significantly higher in the S-NO-HSA group than in the HSA group (HSA: 50,934 +/- 1,382 microm3/s; S-NO-HSA: 78,120 +/- 2,348 microm3/s, P < 0.05). Reversible leukocyte adhesion to sinusoidal endothelium, an indicator of the inflammatory response, was significantly reduced in the S-NO-HAS-treated group. The findings of this study in a rat model of hemorrhagic shock suggest that NO substitution by S-NO-HSA during resuscitation attenuates both early and late hepatic microcirculatory disturbances as well as the increase in leukocyte adherence.

Ischemia/reperfusion injury involves a large number of humoral and cellular mediators that activate leukocytes that subsequently migrate to local tissues. Tumor necrosis factor (TNF)-alpha may be one of the most important mediators of this post-shock inflammatory response. In this study, we investigated the influence of a recombinant Type I (55 kDa) TNF-binding protein (TNF-BP) on leukocyte-endothelial interactions in the liver after hemorrhagic shock. Hemorrhagic shock was induced in female Sprague-Dawley rats (40 mmHg for 90 min) and a standardized resuscitation regimen was applied. At the time of resuscitation, animals were treated intravenously with either TNF-BP 4 mg/kg or placebo. The liver microcirculation was investigated using intravital fluorescence microscopy and immunohistochemistry at 5 h and 48 h after reperfusion. At 5 h, treatment with TNF-BP significantly reduced temporary leukocyte adhesion in the liver sinusoids as well as mean adhesion time of leukocytes in the hepatic central vein. In contrast, after 48 h, permanent leukocyte adhesion in the central hepatic vein was significantly reduced in the group receiving TNF-BP, whereas temporary leukocyte adhesion and mean adhesion time did not differ between the two groups. Both types of leukocyte adhesion, rolling adhesion after 5 h and firm adhesion after 48 h, were reduced in the group treated with TNF-BP, thereby suggesting a long-lasting anti-inflammatory effect.

Background: The generation of iron-dependent toxic oxygen radicals during the initial resuscitation from hemorrhagic shock was shown to be a relevant factor for the initiation of the inflammatory cascade. Therefore, this experimental study was designed to evaluate the effects of a deferoxamine-conjugated hydroxyethyl-starch solution (HES-DFO) on oxygen radical induced injury and microcirculatory alterations in the rat liver compared with resuscitation with regular hydroxyethyl-starch, lactated Ringer's solution (RL), or a gelatin-based solution., Methods: After hemorrhage and random assignment to 1 hour of blood-free resuscitation with the aforementioned solutions, hepatic microcirculation and leukocyte adhesion characteristics were assessed by intravital fluorescence microscopy in anesthetized rats. Oxygen radical activity was estimated by determination of glutathione levels in liver homogenate and determination of thiobarbituric acid-reactive substances in plasma as markers of lipid peroxidation., Results: Resuscitation by HES-DFO resulted in restoration of hemodynamic parameters compared with gelatin-based solution and HES. The hepatic microcirculation was severely altered 1 hour after resuscitation from shock in all groups indicated by sinusoidal narrowing and reduced sinusoidal blood flow. HES-DFO, however, attenuated leukocyte adhesion and improved velocity index in sinusoids as well as sinusoidal perfusion. The shock-associated generation of oxygen radicals during resuscitation was prevented by HES-DFO as indicated by restored glutathione and reduced thiobarbituric acid-reactive substances., Conclusion: The results suggest that HES-DFO effectively reduces oxygen radical formation during the initial resuscitation period, thus, attenuating pathologically enhanced leukocyte adhesion and improving hepatic microcirculation.

The relevance of tumor necrosis factor-alpha (TNF-alpha) inducing early inflammatory reactions in the liver after hemorrhagic shock, for example, leukocyte adhesion, has been well described. This study evaluated the anti-inflammatory effects of a monoclonal antibody against TNF-alpha (TN3.19.12) in terms of the time of application, namely, prior to shock induction, at the time of resuscitation, and after resuscitation. The hepatic microcirculation was investigated by intravital fluorescence microscopy in female Sprague-Dawley rats undergoing severe hemorrhagic shock for 60 min and subsequent resuscitation. TN3.19.12 or placebo was given in a randomized and blinded manner either 60 min prior to shock induction, 1 min prior to resuscitation, or 15 min after the onset of resuscitation. The number of firmly adherent leukocytes in the livers of treated animals depended on the time of application of TN3.19.12. Leukocyte adhesion was significantly reduced when TN3.19.12 was given prior to shock induction or at the time of resuscitation and was less effective when administered after the onset of resuscitation. The results further confirm that TNF-alpha initiates very early pathological leukocyte adhesion in the liver 5 h following shock. Inhibition of leukocyte adhesion after shock, however, depends strongly on the time of TNF-alpha blocking. While TN3.19.12 prior to shock induction resulted in most effective attenuation, only very early treatment allowed limitation of posttraumatically increased leukocyte adhesion.

This study was designed to assess the effect of neutrophil inhibitory factor (NIF), a novel specific inhibitor of CD11b/CD18 on hepatic leukocyte trafficking by intravital microscopy 5 h after hemorrhagic shock. Anesthetized rats were instrumented for invasive hemodynamical monitoring. Hemorrhagic shock was induced for 60 min by withdrawal of arterial blood (mean arterial blood pressure = 40 mmHg). Rats were adequately resuscitated for 5 h to achieve a mean arterial blood pressure > 100 mmHg and were randomly assigned to blinded treatment with NIF or placebo control protein administered as a single intravenous bolus (10 mg/kg) at the time of resuscitation. Intrahepatic leukocyte adhesion was evaluated by in vivo fluorescence microscopy. There were no significant differences observed in hemodynamic parameters between the shock groups throughout the study, however, NIF significantly reduced firm leukocyte adhesion in liver sinusoids. The results suggest that NIF may be beneficial in the attenuation of the pathological shock-induced leukocyte adhesion.

Objective: It is well known that the volatile anaesthetics halothane, enflurane and isoflurane alter hepatic blood flow in a dose-dependent manner. However, there are only a few studies investigating the effect of the new anaesthetic desflurane on the hepatic blood flow. In particular no information is available about the influence of desflurane on liver microcirculation. Therefore, the aim of this study was to evaluate the effects of desflurane in comparison to isoflurane and pentobarbital on microcirculation of the liver in vivo using intravital fluorescence microscopy., Materials: 18 female Sprague-Dawley rats were anaesthetised with pentobarbital sodium, tracheotomised and mechanically ventilated using a rodent ventilator. A midline laparotomy was performed for later intravital microscopy of the liver. At the beginning of the one-hour ventilation period the animals were assigned to one of the following groups: isoflurane 0.75 MAC, desflurane 0.75 MAC and pentobarbital group. Animals of the pentobarbital group received additionally 25 mg/kg pentobarbital intravenously. After 60 min of ventilation and continuous monitoring of the systemic circulation the hepatic microcirculation was investigated by intravital fluorscence microscopy., Results: Mean arterial blood pressure decreased slightly in the isoflurane and the desflurane groups compared to the pentobarbital group. Neither isoflurane nor desflurane did affect the sinusoidal diameters or the sinusoidal blood flow compared to the pentobarbital group., Conclusion: Hepatic microcirculation is not affected by one-hour anaesthesia with 0.75 MAC isoflurane or desflurane in comparison to pentobarbital.

Tumor necrosis factor (TNF) plays a well known role during the development of multiple organ failure, in part due to its role for the expression of adhesion molecules on endothelial cells, thereby contributing to inflammatory reactions. The purpose of this study was to investigate the effects of TNF on leukocyte-endothelial interactions in the liver as a key organ during the systemic inflammatory response syndrome. In Sprague-Dawley rats (n = 6/group) hemorrhagic shock was induced by reduction of the mean arterial blood pressure (MAP) to 40 mmHg for 45 min; resuscitation was initiated by retransfusion of shed blood (60%) and Ringer's lactate. At 1 and 5 h after resuscitation, intravital microscopy of the liver was performed after injection of acridine orange as marker of leukocytes in sham-control animals and in shock animals pretreated with anti-TNF monoclonal antibody (2 mg/kg b.w. TN3; Celltech, Slough, UK) or NaCl .9% 2 h prior to shock induction, respectively. At constant systemic hemodynamic conditions in all groups (e.g., normal MAP), sinusoidal diameters and sinusoidal blood flow were comparably decreased to approximately 75% of control values in all shock groups. Significant differences were observed particularly in respect to permanent adherent leukocytes with 31.8 +/- 4.7% in the shock/NaCl group and 20.7 +/- 2.6% (mean +/- S.E., p < .05) in the shock/TN3 group 5 h after resuscitation following hemorrhagic shock. Consistently higher adhesion rates were observed in the portal regions compared to pericentral regions of the liver lobules.(ABSTRACT TRUNCATED AT 250 WORDS)

The application of radical scavengers reduces reperfusion injury of liver grafts despite the natural occurrence of cellular defense mechanisms enabling the cell to tolerate moderate oxidant stress without further cell damage. The glutathione peroxidase mechanism of the liver serves to reduce hydroxyl radical-induced lipid peroxidation by releasing reduced glutathione from intracellular stores. There is evidence that the application of cysteine-providing amino acids for glutathione synthesis could maintain or even increase liver glutathione. Therefore, the purpose of this study was to evaluate the effect of N-acetylcysteine (NAC) on oxidative stress-induced reperfusion injury after liver transplantation. This was done by applying intravital microscopy. Livers from female Sprague-Dawley rats weighing 220-260 g were stored for 20 h in University of Wisconsin (UW) solution and transplanted orthotopically using the cuff technique. Donors were given 150 mg/kg body weight NAC i.v. or placebo in a blind, random fashion 6 h prior to harvesting, followed by two injections of 50 mg/kg body weight, 4 and 2 h before explantation. In additional experimental groups, recipients were given a bolus of 83 mg/kg body weight NAC or placebo at the beginning of the recipient operations, 1 min prior to reperfusion, and 60 min after surgery. Ninety minutes after transplantation, intravital microscopy was applied and five liver lobules were recorded for 30 s after injection of acridine orange, a fluorescent leukocyte marker. Sinusoidal perfusion, sinusoidal width, and leukocyte adhesion, as well as reduced and oxidized glutathione, were determined in all livers.(ABSTRACT TRUNCATED AT 250 WORDS)

The unique arrangement of large numbers of fixed tissue macrophages, endothelial, and parenchymal cells along hepatic sinusoids as well as their key role in the acute phase response makes the liver a primary target organ in endotoxemia. Pathogenesis of hepatic failure in endotoxemia is incompletely understood, but microcirculatory failure as well as leukocyte-endothelial interaction in response to inflammatory mediators may relate to it. Using intravital fluorescence microscopy, sinusoidal widths, leukocyte flow velocity, and sublobular leukocyte (white blood cell (WBC)) adhesion characteristics 1 h after randomized intravenous application of 0, 0.1, 1, or 5 mg/kg b.w. Escherichia coli endotoxin O 111 B4 (ETX) were evaluated in female Sprague-Dawley rats (n = 6-8/group). Whereas the bolus injection of ETX caused only minor concurrent macrohemodynamic effects, a significant increase of permanent WBC adhesion especially in periportal areas (0 mg, 2.1 +/- 0.7%; 0.1 mg, 16.2 +/- 3.6%**; 1 mg, 15.5 +/- 1.0%**; 5 mg, 13.2 +/- 2.3%* (**p < .01, *p < .05, compared to vehicle)) was found in all groups 60 min after ETX challenge. In contrast, an increase of WBC margination in midzonal and pericentral regions was only seen with the higher doses of 1 or 5 mg/kg ETX, respectively. The sublobular pattern of WBC margination is consistent with the concept of regulation of WBC adhesion by inflammatory mediators released by lipopolysaccharide-stimulated Kupffer cells in vivo. We propose that overwhelming the detoxifying capacity of predominantly periportally located Kupffer cells with large amounts of ETX may lead to activation of pericentral-located resting macrophages paralleled by a rise of adhering leukocytes.

Endothelin-1 (ET-1), a vasoactive peptide, causes a significant rise in portal vein pressure, which is most likely a result of severe vasoconstriction in the liver. In this study, the effect of ET-1 on sinusoidal vasoconstriction in the liver after ischemia and reperfusion was directly investigated using intravital microscopy. In anesthetized female Sprague Dawley rats (200-250 g) ischemia of the median and left liver lobes was induced for 90 min by temporary ligation of the left pedicle. After declamping and a 90-min reperfusion period, the livers were exposed for intravital microscopy. Using a Nikon MM-11 fluorescence microscope (545 nm, 330x), a CCD camera (Cohu FK 6990), and a SVHS video recording unit, the hepatic microcirculation was directly investigated. Besides sham groups, two ischemia groups were studied, receiving ET-1 antiserum (anti-ET-1; 0.5 ml; Peptide Inst., Osaka, Japan) or NaCl 0.9% (0.5 ml) 5 min prior to reperfusion of the liver (n = 6/group). Following a transient drop in the mean arterial blood pressure in the anti-ET-1-treated groups, comparable systemic hemodynamic conditions among the four groups were noted during intravital microscopic assessment at the end of the 90-min reperfusion period. Reduction in the sinusoidal diameters during postischemic reperfusion (7.7 +/- 0.5 microm) was prevented by anti-ET-1 treatment (9.6 +/- 0.25 microm; P < 0.01; mean + SEM) back to control values (9.6 +/- 0.32 microm), while most of other microcirculatory parameters did not show significant differences. The results supported further the role of ET-1 in dysregulation of the sinusoidal vascular tone in the liver, e.g., after ischemia and reperfusion.

Introduction: Microcirculatory disturbances and increased adhesion of leukocytes to the hepatic endothelium immediately following hemorrhagic shock have been observed. It is currently discussed, that mediators released by activated macrophages may have regulative functions for these alterations. The aim of the study performed was to investigate the effects of platelet activating factor (PAF) by application of PAF-receptor antagonists in respect to disorders of liver microcirculation and leukocyte adhesion following hemorrhagic shock., Methods: Sprague-Dawley rats, anesthetized with pentobarbital, were exposed to hemorrhagic shock by depression of the mean arterial blood pressure (MABP) to 40 mmHg for 60 min by controlled blood removal. Three hours following adequate volume replacement together with blood retransfusion (60%) and at normalized MABP as well as supranormal cardiac output levels, the livers of the animals were investigated by intravital microscopy in respect to leukocyte adhesion and microcirculation. Evaluation of the microcirculation of 5 liver lobules/animal was performed on SVHS recorded images using a computer-assisted image analysis system. Three shock groups (n = 6 rats) and one sham-operated control group (n = 8) were compared. Shock/NaCl group received 0.1 ml NaCl 0.9% 15 min prior to shock induction and 1 min prior to shock therapy i. v., respectively. Shock/BN group received a total of 10 mg/kg of the PAF-antagonist BN 52021 (Dr. Braquet, Paris) and Shock/WEB group 2 mg/kg of the PAF antagonist WEB 2086 (Boehringer, Ingelheim), respectively in 2 injections with identical volume., Results: The course of hemodynamic parameters MABP and cardiac output were comparable in all 3 shock groups. Metabolic parameters such as acid-base state and hematocrit values did not reveal differences. Evaluation of liver microcirculation indicated in all shock groups a reduction of sinusoidal diameters and a slight increase of velocity of leukocytes. The significantly increased temporary adhesion of leukocytes with an adhesion time shorter than 20s in the shock/NaCl group (adhesion index 154.1 +/- 63.2s/100 leukocytes; mean +/- SD) was reduced significantly by the PAF antagonists BN 52021 (82.2 +/- 24.2) and WEB 2086 (86.0 +/- 30.0). Permanent adhesion with an adhesion time longer than 20s was increased significantly particularly in zone I of the liver acinus (portal region) in all shock groups without specific effects of the PAF antagonists., Conclusions: Liver microcirculation following adequately treated hemorrhagic shock was disturbed, as indicated by narrowed sinusoids and increased adhesion of leukocytes. PAF seems to have no effect on sinusoidal narrowing in this period, however, it seems involved in temporary adhesion of leukocytes. The relevance of these early changes following hemorrhagic shock in respect to the development of organ dysfunction should be further addressed.

Hepatic microcirculation, leukocyte-endothelial interaction, and sinusoidal widths were studied by means of intravital microscopy in a non-heparinized fixed pressure hemorrhagic shock model in the rat. Asanguineous resuscitation was performed either with "adequate" amounts of lactated Ringer's solution (threefold shed volume/30 min) or 4 ml/kg/3 min 7.2% saline/10% Dextran 60 (HSDex) or 4 ml/kg/3 min 7.2% saline/10% hydroxyethylstarch 200/0.62 (HSHes). Hemorrhagic shock and resuscitation was paralleled by significant (P < 0.01) lumenal narrowing of sinusoids that remained largely uninfluenced by the type of fluid used for resuscitation (HSDex: 9.28 +/- 0.56; HSHes: 8.93 +/- 0.29, LR: 8.87 +/- 0.6 microns compared to 12.17 +/- 0.24 microns in controls). Whereas HSHes and LR-therapy resulted in comparably increased leukocyte adhesion to the sinusoidal wall, the dextran-containing solution led to a significant attenuation of leukocyte-endothelial interaction, suggesting involvement of dextran-binding adhesion molecules, e.g., selectins.

Leukocyte-endothelial cell interactions in rat livers were investigated using intravital fluorescence microscopy following hemorrhagic shock (MAP at 40 mm Hg for 60 min) and resuscitation. Thirty minutes after resuscitation, when MAP was higher than 100 mm Hg, sinusoidal perfusion was only slightly reduced (>90% of controls). Firm adhesion of leukocytes increased to 370 +/- 54 leukocytes/mm2 after shock and resuscitation compared to control animals (48 +/- 8/mm2; mean +/- SEM; P < .01). Leukocyte-endothelium adhesion was highest in the portal areas and lowest in midzonal and pericentral regions (relationship:2.0: 1.1:1.0). Pretreatment with dexamethasone (5 mg/kg bw) resulted in a dramatic rise of adherent leukocytes following hemorrhagic shock (920 +/- 62/mm2; P < .001). Pretreatment with ibuprofen (15 mg/kg bw) resulted in a similar increase of adherent leukocytes after hemorrhagic shock (750 +/- 60/mm2; P < .001), while pretreatment with MK 886(10 mg/kg), inhibitor of lipoxygenase pathway, reduced leukocyte adhesion slightly (270 +/- 38/mm2). The results reveal that leukotrienes, e.g., released by activated macrophages, are involved in the regulation of leukocyte adhesion in liver sinusoids following hemorrhagic shock and resuscitation. The negative effect of dexamethasone and ibuprofen on hepatic leukocyte adhesion, however, has to be considered for therapeutic use.

Severe microcirculatory disturbances due to endothelial cell damage and leukocyte adherence during reperfusion of transplanted livers are considered to contribute to early graft failure. Since the degree of reperfusion injury after liver transplantation depends on the length of preservation time and the solution used for preservation, the aim of our study was to assess three solutions with respect to microvascular perfusion and leukocyte adhesion. Therefore, rat livers were stored up to 24 h in Euro-Collins (EC), University of Wisconsin (UW), or histidin-tryphtophan-ketoglutarate (HTK) solutions prior to orthotopic transplantation. The livers were studied in situ 60 min postoperatively using intravital fluorescence video microscopy. Using simple syringe flushing (10 ml), sinusoidal perfusion decreased below 50% in EC preserved livers after 8 h preservation, in HTK preserved livers after 16 h preservation, and remained higher than 70% in livers preserved in UW up to 24 h. Permanent adhesion of leukocytes was increased more rapidly in organs after 1, 8, 16, and 24 h preservation in HTK (16%, 15%, 34%, and 49.7% +/- 4.7%) compared to those preserved in UW (15%, 18%, 17%; and 32.7% +/- 3.3%; P<0.05). Using a 10-fold volumn of the organ weight of HTK solution during the harvesting procedure, with an 8 min equilibration period, sinusoidal perfusion (39.6 +/- 4.7%) and leukocyte adhesion (42.7 +/- 3.1%) were not improved after 24 h. In contrast, equilibration with a volumn of approximately 40-times the liver weight improved sinusoidal perfusion (70.8% +/- 2.7%; P < 0.01) and leukocyte adhesion (24.9% +/- 3.1%; P < 0.01) significantly. Thus, using HTK solution, simple flushing prior to long-term cold storage resulted in microcirculatory disturbances when compared to UW solution. Larger volumns of HTK solution with an additional equilibration period of 8 min, however, reduced leukocyte adhesion and improved sinusoidal perfusion to a similar degree as UW solution.

The purpose of these experiments was to employ video microscopy to identify early pathological changes after orthotopic liver transplantation in the rat. Liver transplantation was performed using the cuff technique. Survival was greater than 90% when livers were stored for 1 hr in Ringer's solution prior to transplantation (survival conditions), whereas all rats died following storage of grafts for 4 hr in cold Euro-Collins solution (nonsurvival conditions). Postoperatively, each recipient animal was anesthetized, the abdomen was opened, and the liver was placed on the stage of an inverted fluorescence microscope equipped with a low-light ISIT video camera. Precautions were taken to prevent the liver surface from drying. The fluorescent dyes fluorescein sodium (1.0 mumol/kg), acridine orange (2.5 mumol/kg), and propidium iodide (1 mumol/kg) were injected intravenously to label hepatocytes, polymorphonuclear leukocytes, and the nuclei of irreversibly damaged cells, respectively. In livers from untransplanted rats, movement of labeled leukocytes through the hepatic sinusoids was smooth and rapid (velocity, 500-550 microns/sec) and margination (adhesion) of cells was minimal (less than 1%). After transplantation, however, velocity was diminished 2-3-fold, and margination was increased to 10% of leukocytes in survival groups and to 40% in nonsurvival groups 4 hr postoperatively. In the nonsurvival groups, irreversible cell death detected by propidium iodide fluorescence was minimal 15 min after transplantation--however, massive cell damage was detected 4 hr postoperatively. In addition, serum transaminases and necrosis were higher at 4 hr than 15 min postoperatively. Taken together, these data demonstrate that leukocyte margination increases following orthotopic liver transplantation and is followed rapidly by cell death. These events likely play a role in the mechanism of early graft failure following transplantation.

• L-FABP is a novel biomarker for the early detection of abdominal injury and of hemorrhagic shock. • L-FABP is specific in the detection of an injury of the kidney and liver. • NGAL is a novel biomarker for the detection of abdominal injury and hemorrhagic shock. • NGAL failed to be specific in the detection of an injury of the liver and/or the kidney. Delayed diagnosis of abdominal injuries and hemorrhagic shock leads to secondary complications and high late mortality in severely traumatized patients. The liver fatty acid-binding protein (L-FABP) is expressed in intestine, liver and kidney; the neutrophil gelatinase-associated lipocalin (NGAL) in colon and kidney. We hypothesized that l -FABP is an early biomarker for abdominal injury and hemorrhagic shock and that l -FABP and NGAL are specific markers for detection of liver and/or kidney injuries. Traumatized patients with an age ≥18 years and an abdominal injury (AIS abd ≥2), independently from Injury Severity Score (ISS), were prospectively included from 04/2018 to 05/2021. 68 patients had an abdominal injury ("Abd") and 10 patients had an abdominal injury with hemorrhagic shock ("HS Abd"). 41 patients without abdominal injury and hemorrhagic shock but with an ISS ≥ 25 ("noAbd") were included as control group. Four abdominal subgroups with isolated organ injuries were defined. Plasma l -FABP and NGAL levels were measured at admission (ER) and up to two days post-trauma. All patient groups had a median ISS≥25. In ER, median l -FABP levels were significantly higher in "HS Abd" group (1209.2 ng/ml [IQR=575.2–1780.3]) compared to "noAbd" group (36.4 ng/ml [IQR=14.8–88.5]), and to "Abd" group (41.4 ng/ml [IQR=18.0–235.5]), p <0.001. In matched-pair-analysis l -FABP levels in the group "Abd" were significantly higher (108.3 ng/ml [IQR=31.4–540.9]) compared to "noAbd" (26.4 ng/ml [IQR=15.5–88.8]), p = 0.0016. l -FABP correlated significantly with clinical parameters of hemorrhagic shock; the optimal cut-off level of l -FABP for detection was 334.3 ng/ml (sensitivity: 90%, specificity: 78%). Median l -FABP-levels were significantly higher in patients with isolated liver or kidney injuries and correlated significantly with AST, ALT and creatinine value. Median NGAL levels in the ER were significantly higher in "HS Abd" group (115.9 ng/ml [IQR=90.6–163.8]) compared to "noAbd" group (58.5 ng/ml [IQR=41.0–89.6], p <0.001) and "Abd" group (70.5 ng/ml [IQR=53.3–115.5], p <0.05). The group "Abd" showed significant higher median NGAL levels compared to "noAbd", p = 0.019. NGAL levels correlated significantly with clinical parameters of hemorrhagic shock. : L-FABP and NGAL are novel biomarkers for detection of abdominal trauma and hemorrhagic shock. l -FABP may be a useful and promising parameter in diagnosis of liver and kidney injuries, NGAL failed to achieve the same. [ABSTRACT FROM AUTHOR]