Use of Vasopressor Increases the Risk of Mortality in Traumatic Hemorrhagic Shock: A Nationwide Cohort Study in Japan.

OBJECTIVES: To evaluate the possible association of vasopressor use with mortality in traumatic hemorrhagic shock patients. DESIGN: Retrospective cohort study. SETTING: Traumatic hemorrhagic shock patients at 260 emergency hospitals in Japan between 2004 and 2015. PATIENTS: Three-thousand five-hundred fifty-one traumatic hemorrhagic shock patients who had systolic hypotension (< 90 mm Hg) on arrival at the emergency department and a blood transfusion received within the first 24 hours. INTERVENTIONS: The use of vasopressor for traumatic hemorrhagic shock within the first 24 hours. MEASUREMENTS AND MAIN RESULTS: Among 236,698 trauma patients, 3,551 were included in the study. Overall, 198 of 459 patients (43%) in the vasopressor+ group expired compared with 481 of 3,092 patients (16%) in the vasopressor- group. Use of vasopressor had an odds ratio of 2.172 (95% CI, 1.666-2.833) for in-hospital mortality adjusted for age, gender, year of onset, cause of injury, mechanism of injury, vital signs at the emergency department, Injury Severity Score, use of prehospital IV fluid, and volume of blood transfusion within the first 24 hours. In the propensity score-matched cohort and two subgroup analyses (massive transfusion and survivable injury models), use of vasopressor was associated with higher mortality (odds ratio, 2.168; 95% C, 1.442-3.320), (odds ratio, 2.029; 95% CI, 1.414-2.911; massive transfusion model), and (odds ratio, 1.959; 95% CI, 1.364-2.814; survivable injury model). CONCLUSIONS: Use of vasopressor for traumatic hemorrhagic shock was associated with mortality after controlling for biases (trauma severity; volume of fluid resuscitation).

Effects of Quercetin in a Rat Model of Hemorrhagic Traumatic Shock and Reperfusion.

BACKGROUND: We hypothesized that treatment with quercetin could result in improved hemodynamics, lung inflammatory parameters and mortality in a rat model of hemorrhagic shock. METHODS: Rats were anesthetized (80 mg/kg ketamine plus 8 mg/kg xylazine i.p.). The protocol included laparotomy for 15 min (trauma), hemorrhagic shock (blood withdrawal to reduce the mean arterial pressure to 35 mmHg) for 75 min and resuscitation by re-infusion of all the shed blood plus lactate Ringer for 90 min. Intravenous quercetin (50 mg/kg) or vehicle were administered during resuscitation. RESULTS: There was a trend for increased survival 84.6% (11/13) in the treated group vs. the shock group 68.4% (13/19, p > 0.05 Kaplan-Meier). Quercetin fully prevented the development of lung edema. The activity of aSMase was increased in the shock group compared to the sham group and the quercetin prevented this effect. However, other inflammatory markers such as myeloperoxidase activity, interleukin-6 in plasma or bronchoalveolar fluid were similar in the sham and shock groups. We found no bacterial DNA in plasma in these animals. CONCLUSIONS: Quercetin partially prevented the changes in blood pressure and lung injury in shock associated to hemorrhage and reperfusion.

Beneficial effect of cyclosporine A on traumatic hemorrhagic shock.

BACKGROUND: Vascular hyporeactivity plays an important role in severe trauma and shock. We investigated the beneficial effect of cyclosporine A (CsA) on traumatic shock and its relationship to vascular reactivity improvement and mitochondrial permeability transition pore (MPTP). MATERIALS AND METHODS: Sodium pentobarbital-anesthetized rats were used to induce traumatic hemorrhagic shock by left femur fracture and hemorrhage, the beneficial effects of CsA (1, 5, and 10 mg/kg, intravenously) on animal survival, cardiovascular function, tissue blood perfusion, and mitochondrial function of vital organs were observed. In addition, hypoxia-treated vascular smooth muscle cells from normal rats were used to investigate the relationship of this beneficial effect of CsA to Rho-associated serine/threonine kinase (ROCK) and protein kinase C. RESULTS: CsA prolonged the survival time and increased the 24-h survival rate of traumatic hemorrhagic shock (31%, 56%, and 56% in 1, 5, and 10 mg/kg CsA group versus 25% in lactated Ringer solution group). Five milligrams per kilogram of CsA had the best effect, which stabilized and improved the hemodynamics, increased the tissue blood flow, and improved the liver and kidney function including its mitochondrial function in shock rats. CsA had no significant influences on the production of inflammatory mediators and cardiac output after traumatic hemorrhagic shock. Further results indicated that CsA significantly improved the vascular constriction and dilation reactivity of superior mesenteric artery to norepinephrine and acetylcholine, which was antagonized by ROCK inhibitor, Y27632, but not by protein kinase C inhibitor, staurosporine. Further studies showed that CsA restored hypoxia-induced decrease of ROCK activity and inhibited the opening of MPTP in hypoxia-treated vascular smooth muscle cells. CONCLUSIONS: CsA is beneficial for the treatment of traumatic hemorrhagic shock. The mechanism is mainly through improving the vascular reactivity, stabilizing the hemodynamics, and increasing tissue perfusion. This beneficial effect of CsA is related to the inhibitory effect of CsA on MPTP opening. ROCK is an important regulator molecule in this process.

Hypertonic saline in the traumatic hypovolemic shock: meta-analysis.

BACKGROUND: A wealth of evidence from animal experiments has indicated that hypertonic saline (HS) maybe a better choice for fluid resuscitation in traumatic hypovolemic shock in comparison with conventional isotonic saline. However, the results of several clinical trials raised controversies on the superiority of fluid resuscitation with HS. This meta-analysis was performed to better understand the efficacy of HS in patients with traumatic hypovolemic shock comparing with isotonic saline. MATERIALS AND METHODS: According to the search strategy, we searched the PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, which was completed on October 2013. After literature searching, two investigators independently performed the literature screening, assessment of quality of the included trials, and data extraction. Disagreements were resolved by consensus or by a third investigator if needed. The outcomes included mortality, blood pressure, fluid requirement, and serum sodium. RESULTS: Six randomized controlled trials were included in the meta-analysis. The pooled risk ratio for mortality at discharge was 0.96 (95% confidence interval [CI], 0.82-1.14), whereas the pooled mean difference for the change in systolic blood pressure from baseline and the level of serum sodium after infusion was 6.47 (95% CI, 1.31-11.63) and 7.94 (95% CI, 7.38-8.51), respectively. Current data were insufficient to evaluate the effect of HS on the fluid requirement for the resuscitation. CONCLUSIONS: The present meta-analysis was unable to demonstrate a clinically important improvement in mortality after the HS administration. Moreover, we observed HS administration maybe accompanied with significant increase in blood pressure and serum sodium.

The use of the Revised Trauma Score as an entry criterion in traumatic hemorrhagic shock studies: data from the DCLHb clinical trials.

INTRODUCTION: The Revised Trauma Score (RTS) has been proposed as an entry criterion to identify patients with mid-range survival probability for traumatic hemorrhagic shock studies. HYPOTHESIS/PROBLEM: Determination of which of four RTS strata (1-3.99, 2-4.99, 1-4.99, and 2-5.99) identifies patients with predicted and actual mortality rates near 50% for use as an entry criterion in traumatic hemorrhagic shock clinical trials. METHODS: Existing database analysis in which demographic and injury severity data from two prior international Diaspirin Cross-Linked Hemoglobin (DCLHb) clinical trials were used to identify an RTS range that could be an optimal entry criterion in order to find the population of trauma patients with mid-range predicted and actual mortality rates. RESULTS: Of 208 study patients, the mean age was 37 years, 65% sustained blunt trauma, 49% received DCLHb, and 57% came from the European Union study arm. The mean values were: ISS, 31 (SD = 18); RTS, 5.6 (SD = 1.8); and Glasgow Coma Scale (GCS), 10.4 (SD = 4.8). The mean TRISS-predicted mortality was 34% and the actual 28-day mortality was 35%. The initially proposed 1-3.99 RTS range (n = 41) had the highest predicted (79%) and actual (71%) mortality rates. The 2-5.99 RTS range (n = 79) had a 62% predicted and 53% actual mortality, and included 76% blunt trauma patients. Removal of GCS <5 patients from this RTS 2-5.99 subgroup caused a 48% further reduction in eligible patients, leaving 41 patients (20% of 208 total patients), 66% of whom sustained a blunt trauma injury. This subgroup had 54% predicted and 49% actual mortality rates. Receiver operator curve (ROC) analysis found the GCS to be as predictive of mortality as the RTS, both in the total patient population and in the RTS 2-5.99 subgroup. CONCLUSION: The use of an RTS 2-5.99 inclusion criterion range identifies a traumatic hemorrhagic shock patient subgroup with predicted and actual mortality that approach the desired 50% rate. The exclusion of GCS <5 from this RTS 2-5.99 subgroup patients yields a smaller, more uniform patient subgroup whose mortality is more likely related to hemorrhagic shock than traumatic brain injury. Future studies should examine whether the RTS or other physiologic criteria such as the GCS score are most useful as traumatic hemorrhagic shock study entry criteria.

Clinical effects of intensive insulin therapy treating traumatic shock combined with multiple organ dysfunction syndrome.

The therapeutic effects of intensive insulin therapy in treatment of traumatic shock combined with multiple organ dysfunction syndrome (MODS) were investigated. A total of 114 patients with traumatic shock combined with MODS were randomly divided into two groups: control group (n=56) treated with conventional therapy, and intensive insulin therapy group (n=58) treated with conventional therapy plus continuous insulin pumping to control the blood glucose level at range of 4.4-6.1 mmol/L. White blood cells (WBC) counts, prothrombin time (PT), serum creatinine (SCr), alanine aminotransferase (ALT), serum albumin and PaO(2) were measured before and at the day 1, 3, 5, 7 and 14 after treatment. The incidence of gastrointestinal dysfunction, the incidence of MODS, hospital stay and the mortality were also observed and compared. After intensive insulin therapy, the WBC counts, SCr, ALT and PT were significantly reduced (P<0.05), but the level of serum albumin was significantly increased (P<0.05) at the day 3, 5, 7 and 14. In the meantime, the PaO2 was significantly elevated at the day 3, 5 and 7 (P<0.01) after intensive insulin therapy. The incidence of gastrointestinal dysfunction, the incidence of MODS, the length of hospital stay and the mortality were markedly decreased (P<0.01). The results suggest early treatment with intensive insulin therapy is effective for traumatic shock combined with MODS and can decrease the length of hospital stay and the mortality.

[Tranexamic acid therapy decreases mortality of traumatic hemorrhagic shock]. / El ácido tranexámico disminuye la mortalidad del shock hemorrágico traumático.

The CRASH 2, a randomized, double-blind, controlled trial, that enrolled 20,211 adult trauma patients, has shown that the administration of tranexamic acid significantly reduces all-cause mortality and that specifically associated with severe blood loss as well. We consider it a significant therapeutic advance, because, for the first time, a drug has been demonstrated to safely diminish mortality due to traumatic bleeding shock. On the basis of these results, and the high rate of death due to traumatic bleeding, we suggest that tranexamic acid should be considered for compassionate use in bleeding trauma patients prior to its definitive approval for this medical condition.

Diaspirin cross-linked hemoglobin infusion did not influence base deficit and lactic acid levels in two clinical trials of traumatic hemorrhagic shock patient resuscitation.

BACKGROUND: Diaspirin cross-linked hemoglobin (DCLHb) has demonstrated a pressor effect that could adversely affect traumatic hemorrhagic shock patients through diminished perfusion to vital organs, causing base deficit (BD) and lactate abnormalities. METHODS: Data from two parallel, multicenter traumatic hemorrhagic shock clinical trials from 17 US Emergency Departments and 27 European Union prehospital services using DCLHb, a hemoglobin-based resuscitation fluid. RESULTS: In the 219 patients, the mean age was 37.3 years, 64% of the patients sustained a blunt injury, 48% received DCLHb resuscitation, and the overall 28-day mortality rate was 36.5%. BD data did not differ by treatment group (DCLHb vs. normal saline [NS]) at any time point. Study entry BD was higher in patients who died when compared with survivors in both studies (US: -14.7 vs. -9.3 and European Union: -11.1 vs. -4.1 mEq/L, p < 0.003) and at the first three time points after resuscitation. No differences in BD based on treatment group were observed in either those who survived or those who died from the hemorrhagic shock. US lactate data did not differ by treatment group (DCLHb vs. NS) at any time point. Study entry lactates were higher in US patients who ultimately died when compared with survivors (82.4 vs. 56.1 mmol/L, p < 0.003) and at all five postresuscitation time points. No lactate differences were observed between DCLHb and NS survivors or in those who died based on treatment group. CONCLUSIONS: Although patients who died had more greatly altered perfusion than those who survived, DCLHb treatment of traumatic hemorrhagic shock patients was not associated with BD or lactate abnormalities that would indicate poor perfusion.

Effect of intravenous atrial natriuretic peptide on pulmonary dysfunction and renal function following burn shock.

BACKGROUND: The typical response to burn stress causes burn shock, followed by a diuretic phase; however, fluid management remains crucial in this phase in the treatment of the elderly, patients with preexisting cardiac or renal diseases, and patients developing acute renal failure. We studied the effects of human atrial natriuretic peptide (hANP), which is a renal vasodilator, natriuretic, and inhibitor of renin secretion, on renal function in these patients with burn injuries. METHODS: Thirty-three severely burned patients (44.8% +/- 20.6% total burn surface area) with prolonged cardiovascular overload and pulmonary edema after burn shock receiving a continuous infusion of hANP (0.025 microg/kg/min and 0.05 microg/kg/min, hANP group) were compared with control (no-hANP group, n = 25). Vital signs, urine output (UO) and blood gas analysis before and 72 hour after the start of hANP were recorded. Creatinine clearance, free water clearance, and fractional excretion of sodium were also calculated. RESULTS: Sixteen (48%) patients were elderly, over 80 years old. Twenty (60%) had preexisting cardiovascular disease, renal insufficiency, or diabetes. hANP infusion increased UO in 25 (66%) cases and improved oxygenation in 31 (82%) cases. Treatment with hANP increased creatinine clearance, fractional excretion of sodium, and UO, except in four cases that had already progressed to complete renal failure before the infusion of hANP. CONCLUSIONS: Intravenous hANP seems to be effective for postresuscitative pulmonary dysfunction and renal function after burn shock in the vulnerable elderly, or patients with preexisting disease, suggesting that it could be valuable in facilitating fluid management in the acute phase in severely burned patients.

[The changes of content of TNF-alpha, nitric oxide and FeS-NO in patients blood with traumatic shock under Plaferon LB influence].

There were examined 40 patients with traumatic shock and 10 healthy blood-donor (1-st group). The patients were divided into two groups: patients with traumatic shock based on standard program of intensive therapy and patients with traumatic shock based on standard program of intensive therapy plus Plaferone LB. The blood test was made on 1st and 5th day of stationary treatment. TNF-alpha was examined in blood plasma by immunophermetic method and NO, FeS-NO by electro-paramagnetic resonance method. It was revealed, that Plapherone LB has no affect on TNF-alpha concentration, but it modulates NO concentration.

[The condition of oxidation-antioxidation balance of kidney and suprarenal tissue in experimental traumatic shock with white rats and the influence of Plaferon LB].

The aim of the work is the study of the oxidation-ant oxidation balance of kidney and suprarenal tissue and the influence on them of Plapherone LB preparation. The objects for experiment were 30 white rats which weigh was about 200gr. The traumatic shock was reproduced according to Kennon. White rats were divided into two groups. In 15 minutes after shock intraperitonealy were made: first group - 0,3 ml of physiologic solution, second group - Plapherone LB 0,06 mg on 0,3 mg of physiologic solution. Separately was studied control group of animals. The tissues were studied by the method of electronic paramagnet resonance on RE-1304 radiometer (Russia). The rough upset of oxidation-antioxidation balance was revealed. The use of Plapherone LB in this case promotes the optimization of these changes.

[Influence of antioxidants under polytrauma during traumatic sickness].

To study protective effect of Plapheron LB during grave traumatic sickness. Studied 94 patients with grave polytrauma, who were divided in to two groups of 47 patients. To I-st group was prescribed ordinary program of intensive therapy and to the II-nd group of patients additionally to the ordinary program of intensive therapy was made Plapheron LB in dose of 0.028 mg/kg two times a day sublingually during ten days. Grave condition of the patient was fixed by RTS scale and grave of shock by Skinner scale. Stated that each group was different in grave traumatic and shock conditions. Separately was studied group of health patients. The study was held by the method of electro-paramagnetic resonance of venous blood to admitted to hospital patients and on fifth day of intensive therapy. Noted: NO, FeS-NO, Fe(3+)-transpherin, Fe(2+) and Met-Hb. From immunology cytokin TNF-alpha was studied by the method of immunopherment. Results of study and discussion: Plapheron LB promotes decrease of the process of peroxide oxidation of lipids, increases activation of antioxidant ferments, stimulates production of nitric oxide and decreases the quantity of pyoinflammatory complication from those organs and systems which has no frequent effect of medical manipulation.

Calcium entry inhibition during resuscitation from shock attenuates inflammatory lung injury.

Trauma and hemorrhagic shock (T/HS) induce a systemic inflammatory response syndrome (SIRS). Neutrophils (polymorphonuclear leukocytes [PMN]) and other cells involved in acute lung injury (ALI) are activated by Ca2+ entry. Thus, inhibiting Ca2+ entry might attenuate post-traumatic lung injury. Inhibiting voltage-operated (L-type) Ca2+ channels during shock could cause cardiovascular collapse, but PMN are "nonexcitable" cells, lack L-type channels, and mobilize Ca2+ via nonspecific channels. We previously showed that PMN Ca2+ entry requires sphingosine 1-phosphate synthesis by sphingosine kinase and that both sphingosine kinase inhibition and blockade of nonspecific channels attenuate ALI when begun before shock. Pretreatment for clinical injuries, however, is impractical. Therefore, we now studied whether Ca2+ entry inhibition that begun during resuscitation from T/HS could attenuate SIRS and ALI without causing hemodynamic compromise. Male Sprague-Dawley rats underwent laparotomy and fixed-pressure shock (mean arterial pressure, 35 +/- 5 mmHg; 90 min). Sphingosine kinase inhibition or nonspecific Ca2+ channel inhibition was begun after resuscitation with 10% of shed blood. We then studied in vivo PMN activation and associated lung injury in the presence or absence of Ca2+ entry inhibition. Neither treatment worsened shock. Each treatment decreased CD11b expression, respiratory burst, PMN p38 MAP-kinase phosphorylation, PMN sequestration, and lung capillary leak in vivo. The similar results seen with two different forms of inhibition strengthen the conclusion that the biological effects seen were specific for calcium entry inhibition. Ca2+ entry inhibition is a candidate therapy for management of lung injury after shock.

Developing alternative strategies for the treatment of traumatic haemorrhagic shock.

PURPOSE OF REVIEW: The optimal strategy of stabilizing haemodynamic function in uncontrolled traumatic haemorrhagic shock states is unclear. Although fluid replacement is established in controlled haemorrhagic shock, its use in uncontrolled haemorrhagic shock is controversial, because it may worsen bleeding. RECENT FINDINGS: In the refractory phase of severe haemorrhagic shock, arginine vasopressin has been shown to be beneficial in selected cases due to an increase in arterial blood pressure, shift of blood away from a subdiaphragmatic bleeding site towards the heart and brain, and decrease in fluid resuscitation requirements. Especially in patients with severe traumatic brain injury, rapid stabilization of cardiocirculatory function is essential to ensure adequate brain perfusion and thus to prevent neurological damage and to improve outcome. In addition, despite wide distribution of highly developed and professional emergency medical systems in western industrialized countries, survival chances of patients with uncontrolled traumatic haemorrhagic shock in the prehospital setting are still poor. SUMMARY: A multicenter, randomized, controlled, international clinical trial is being initiated to assess the effects of arginine vasopressin (10 IU) vs. saline placebo in prehospital traumatic haemorrhagic shock patients, not responding to standard shock treatment, being managed by helicopter emergency medical services [vasopressin in traumatic haemorrhagic shock (VITRIS.at) study].

Androstenetriol immunomodulation improves survival in a severe trauma hemorrhage shock model.

BACKGROUND: Traumatic shock activates the hypothalamic-pituitary-adrenal axis (HPA) to mediate a cascade of defensive mechanisms that often include overwhelming inflammatory response and immunosuppression, which may lead to multiple organ failure. Androstenetriol (5 androstene, 3beta, 7beta, 17beta triol-AET) is a metabolite of dehydroepiandrosterone that markedly up regulates host immune response, prevents immune suppression, modulates inflammation and improves survival after lethal infections by pathogens and lethal radiation. HYPOTHESIS: AET-induced immune modulation will improve survival in a conscious rodent model of traumatic shock. METHODS: A relevant traumatic shock rodent model that applies to both combat and civilian sectors was used. After creation of a midline laparotomy (soft tissue trauma), animals were hemorrhaged to a mean arterial pressure of 35-40 mm Hg. Resuscitation was initiated sixty minutes later with crystalloid fluid and packed red blood cells and animals were observed for two days. In a randomized and blinded fashion, AET or vehicle was administered subcutaneously at the beginning of resuscitation. RESULTS: In the vehicle group 5 out of 16 animals survived, (31%). In contrast, 9 out of 13 animals who received AET survived (69%), (Fisher Exact Test p < 0.05). Survival in the AET treatment group was associated with reduced levels of IL-6, IL-10, and IL-18, and enhanced IFN-gamma and IL-2 levels. CONCLUSION: : The results indicate that AET provides a significant protective effect and improves survival in a clinically relevant model of traumatic hemorrhagic shock. AET protective effects are associated with an elevation of Th1 and reduction of Th2 cytokines.

[The role of desensitization of glucocorticoid receptors in the development of vascular resistance to endogenous vasoconstrictors in traumatic shock].

The fact that the activity of cytosol glucocorticoid receptors decreases in shock have been shown before [Golikov P. P. et al., 2001]. The connection between the development of vascular hyporeactivity to endogenous vasoconstrictors and desensitization of glucocorticoid receptors was studied in this investigation. On Kenton traumatic model in a rat experiment, it was shown that the strength of the isometric constriction of the isolated aorta in response to angiotensin II, endothelin-1, phenylephrine, noradrenaline, and vasopressin falls on the second day after a severe mechanical injury (3.3, 2.1, 1.7, 1.6, and 1.5 times, respectively; p < 0.01). On the contrary, the strength of the constriction in response to serotonin increases more then twice. Artificial desensitization of glucocorticoid receptors by long-term administration of dexamethasone (3 mg per kg during five days) results in similar changes of vascular reactivity i.e. a 2.5, 2, 7, and 1.4-fold decrease in the strength of aortal constriction in response to angiotensin II, vasopressin, and endothelin-1, respectively. The strength of the constriction in response to serotonin tended to increase as well. Carbahol-induced relaxation of the aorta pre-constricted with noradrenaline did not change compared with control, being 70 to 80%, both in shock and after desensitization of glucocorticoid receptors with dexamethasone. Presumably, the pathogenetic mechanism of pressor reaction suppression, connected with a decrease in cytosol glucocorticoid receptor activity and thus with inhibition of glucocorticoid-induced expression of the membrane receptors of endogenous vasoconstrictors, is realized in traumatic shock together with other mechanisms.

Allicin ameliorates intraintestinal bacterial translocation after trauma/hemorrhagic shock in rats: The role of mesenteric lymph node dendritic cell.

BACKGROUND: Intestinal dendritic cells play important roles in regulating the function of the intestinal immune barrier and the intestinal bacterial translocation. In this study, we aim to investigate the effects of allicin on the function of mesenteric lymph node-dendritic cells after trauma/hemorrhagic shock. METHODS: One hundred and eight-four Sprague-Dawley rats were randomly assigned into a sham group (n = 46), sham + allicin group (n = 46), trauma/hemorrhagic shock group (n = 46), and trauma/hemorrhagic shock + allicin group (n = 46). Studies were performed on an in vivo model of spontaneously breathing rats with induced trauma/hemorrhagic shock. Allicin was diluted in resuscitation fluid and was administered through the right jugular vein. Flow cytometry was used to determine the expression of CD80, CD86, and major histocompatibility complex II (MHC II) on the surface of mesenteric lymph node-dendritic cells, as well as apoptosis. Intraintestinal bacterial translocation was monitored by using bioluminescent citrobacter. Intestinal permeability tests were conducted by using both FITC-Dextran and Ussing-Chember assay. RESULT: CD80 and MHC-II expression levels were downregulated in the trauma/hemorrhagic shock group compared with the sham and sham + allicin groups; however, the expression was upregulated after allicin treatment. Also, allicin could ameliorate the trauma/hemorrhagic shock-induced increase in early apoptosis of mesenteric lymph node-dendritic cells. A significant increase was observed in the permeability of the intestinal barrier after severe traumatic shock, along with an obvious intraintestinal bacterial translocation to mesenteric lymph node. No difference was noticed in the bacterial translocation in mesenteric lymph node in the trauma/hemorrhagic shock group compared with trauma/hemorrhagic shock + allicin group (P = .589), which indicated allicin could not block bacterial translocation into mesenteric lymph node after trauma/hemorrhagic shock. However, it may increase the capacity of mesenteric lymph node to block intraintestinal bacterial translocation to extraintestinal organs as a statistical difference was noticed in the bacterial translocation in liver, blood, and spleen between trauma/hemorrhagic shock and trauma/hemorrhagic shock + allicin groups (P < .05). CONCLUSION: Trauma/hemorrhagic shock resulted in a decrease of mature mesenteric lymph node-dendritic cells. Allicin treatment could block intraintestinal bacterial translocation through increasing the immunologic barrier function of mesenteric lymph node by modulating dendritic cells maturation.

Amiloride moderates increased gut permeability and diminishes mesenteric lymph-mediated priming of neutrophils in trauma/hemorrhagic shock.

BACKGROUND: Amiloride, an inhibitor of Na+/H+ exchangers and Na+ channels has been shown recently to ameliorate both gut and lung injury in rats subjected to a combined insult of trauma and hemorrhagic shock (T/HS). We have shown previously that mesenteric lymph duct ligation prevents T/HS-induced lung endothelial injury and neutrophil activation, suggesting that toxic inflammatory factors originating from the gut and carried in the lymph are responsible for the lung injury observed after T/HS. This study investigates whether the protective effect of amiloride against T/HS-induced lung injury was associated with decreased lymph toxicity and gut permeability. METHODS: Male rats subjected to trauma (laparotomy) plus hemorrhagic shock (mean arterial pressure, 30 mm Hgx90 min) (T/HS) or trauma plus sham shock (T/SS) and treated with amiloride or its vehicle had their mesenteric lymph duct catheterized. Mesenteric lymph collected before and after shock was assayed for biologic activity on endothelial cells (cytotoxicity and permeability) and neutrophils (respiratory burst activity). Gut permeability was assessed by monitoring plasma concentrations of the fluorescent dye FITC-dextran after its injection into the ileum. RESULTS: Amiloride administration reduced the capacity of post-shock mesenteric lymph to prime neutrophils for an increased respiratory burst. Amiloride failed to decrease the ability of mesenteric lymph to kill endothelial cells or increase their permeability. Amiloride decreased gut permeability. CONCLUSIONS: The mechanisms of the lung protective effect of amiloride in rats undergoing T/HS may be secondary to decreased neutrophil activation, diminished gut permeability, or an effect on the end organ.