Bacterial translocation and intestinal atrophy after thermal injury and burn wound sepsis.

Bacterial translocation (BT) occurs after thermal injury in rodents in association with intestinal barrier loss. Infection complicating thermal injury may also affect the intestine producing bowel atrophy. To study these relationships, Wistar rats received either 30% scald followed by wound inoculation with Pseudomonas; 30% scald with pair feeding to infected animals; or sham injury as controls. On days 1, 4, and 7 after injury animals were killed with examination of the bowel and culture of the mesenteric lymph nodes (MLN), livers, spleens, and blood. All burned animals demonstrated BT to the MLN on day 1 after injury, but only burn-infected animals had continued BT on days 4 and 7, with progression of BT to the abdominal organs and blood. Burn injury and infection also resulted in significant atrophy of small bowel mucosa temporally associated with continued BT. Thus injury complicated by infection results in prolonged and enhanced bacterial translocation, perhaps due to failure to maintain the mucosal barrier.     

The effect of granulocyte colony-stimulating factor (G-CSF) upon burn-induced defective neutrophil chemotaxis

Severe thermal injury results in impairment of granulocyte production and function. The ability to improve the functional capacity of neutrophils could contribute to a reduced morbidity and mortality from sepsis following thermal injury. Previous studies from this laboratory have shown that rhG-CSF increases the number of femoral marrow granulocyte progenitor cells and circulating neutrophils as well as the survival rate following burn wound infection. The studies reported here examine the effect of in-vivo administration of rhG-CSF on neutrophil chemotaxis following a burn injury and also following superimposed Pseudomonas burn wound sepsis in mice. Casein-elicited peritoneal neutrophils were harvested 72 hours after burn injury and 24 hours after infection. Chemotaxis was assessed using microchemotaxis chambers and 10(-5) M fMet-Phe as a chemoattractant. The number of neutrophils that migrated into the filter was used as an index of directed chemotaxis. Burn injury resulted in depressed chemotaxis compared with sham or sham/G-CSF-treated animals (p less than 0.05). Administration of rhG-CSF to burned animals resulted in a level of neutrophil chemotaxis comparable with that in control animals. The presence of a burn wound infection caused no further impairment of chemotaxis. Administration of rhG-CSF to animals with a burn wound infection resulted in improved chemotaxis compared with sham, burned, and burned/infected animals. The beneficial effect of G-CSF following burn wound infections from this and previous studies appears to be a combination of expanded numbers of myeloid elements and preservation of their function.     

Gastric and small bowel ileus after severe burn in rats: The effect of cyclooxygenase-2 inhibitors

Gastrointestinal (GI) ileus is a common complication after severe burns. Selective cyclooxygenase-2 inhibitors (COX-2i) improved post-operative ileus, but its effect on burn-induced GI dysmotility is unknown. Our aim was to test whether a COX-2i improves gastric emptying (GE) and small bowel transit (SBT) after burn. Experiment on GE: rats were anesthetized and randomized into sham/scald burn, treated/untreated with COX-2i. Six hours after burn, rats received a phenol red meal and were sacrificed 30 min later. Gastric emptying was determined based on the percentage of phenol red recovered in harvested stomachs. Experiment on SBT: rats received a duodenostomy and were scald/sham burned 5 days later. Six hours after burn, rats received a phenol red meal through the duodenostomy catheter and were sacrificed 100 min later. Geometric center (GC) was calculated for SBT. GE was decreased significantly in burned vs. sham animals (p < 0.001). SBT was significantly impaired in burned vs. sham animals (p < 0.001). The COX-2i improved GE in the burn rats but not GE in the control rats or SBT in the burn rats. COX-2i improves burn-induced delayed GE, suggesting the mediation of the latter via the prostaglandin pathway.     

Role of neutrophils in the intestinal alterations associated with thermal injury

We have examined the role of neutrophils in the alterations observed in the intestines of rats subjected to 40 per cent surface area scald injury. Histologically, there was no evidence of neutrophilia in the intestinal tissue, and myeloperoxidase activity in mucosal scrapings was not elevated. The distribution of labelled human neutrophils injected into the burned rats showed no enhancement of uptake in the intestines, although there was increased uptake by the lung. The present data suggest that neutrophil migration may not play a role in the alterations in small intestinal function and morphology seen in burn trauma in the rat, but may be a factor in lung damage associated with thermal injury.     

One-hit wonder: Late after burn injury,granulocytes can clear one bacterial infection but cannot control a subsequent infection

ObjectiveBurn injury induces an acute hyperactive immune response followed by a chronic immune dysregulation that leaves those afflicted susceptible to multiple secondary infections. Many murine models are able to recapitulate the acute immune response to burn injury, yet few models are able to recapitulate long-term immune suppression and thus chronic susceptibility to bacterial infections seen in burn patients. This has hindered the field, making evaluation of the mechanisms responsible for these susceptibilities difficult to study. Herein we describe a novel mouse model of burn injury that promotes chronic immune suppression allowing for susceptibility to primary and secondary infections and thus allows for the evaluation of associated mechanisms.MethodsC57Bl/6 mice receiving a full-thickness contact burn were infected with Pseudomonas aeruginosa 14 days (primary infection) and/or 17 days (secondary infection) after burn or sham injury. The survival, pulmonary and systemic bacterial load as well as frequency and function of innate immune cells (neutrophils and macrophages) were evaluated.ResultsFollowing secondary infection, burn mice were less effective in clearance of bacteria compared to sham injured or burn mice following a primary infection. Following secondary infection both neutrophils and macrophages recruited to the airways exhibited reduced production of anti-bacterial reactive oxygen and nitrogen species and the pro-inflammatory cytokineIL-12 while macrophages demonstrated increased expression of the anti-inflammatory cytokine interleukin-10 compared to those from sham burned mice and/or burn mice receiving a primary infection. In addition the BALF from these mice contained significantly higher level so of the anti-inflammatory cytokine IL-4 compared to those from sham burned mice and/or burn mice receiving a primary infection.ConclusionsBurn-mediated protection from infection is transient, with a secondary infection inducing immune protection to collapse. Repeated infection leads to increased neutrophil and macrophage numbers in the lungs late after burn injury, with diminished innate immune cell function and an increased anti-inflammatory cytokine environment.     

Muscle contractile properties in severely burned rats

Burn induces a sustained catabolic response which causes massive loss of muscle mass after injury. A better understanding of the dynamics of muscle wasting and its impact on muscle function is necessary for the development of effective treatments. Male Sprague–Dawley rats underwent either a 40% total body surface area (TBSA) scald burn or sham burn, and were further assigned to subgroups at four time points after injury (days 3, 7, 14 and 21). In situ isometric contractile properties were measured including twitch tension (Pt), tetanic tension (Po) and fatigue properties. Body weight decreased in burn and sham groups through day 3, however, body weight in the sham groups recovered and increased over time compared to burned groups, which progressively decreased until day 21 after injury. Significant differences in muscle wet weight and protein weight were found between sham and burn. Significant differences in muscle contractile properties were found at day 14 with lower absolute Po as well as specific Po in burned rats compared to sham. After burn, the muscle twitch tension was significantly higher than the sham at day 21. No significant difference in fatigue properties was found between the groups. This study demonstrates dynamics of muscle atrophy and muscle contractile properties after severe burn; this understanding will aid in the development of approaches designed to reduce the rate and extent of burn induced muscle loss and function.     

Cachectin/TNF production in experimental burns and Pseudomonas infection

Burn injury and infection result in significant losses of lean tissue. The cytokine cachectin/tumor necrosis factor has been implicated in this process but is not uniformly detected during infection. We sought to determine the relationship between body composition changes and in vivo hepatic levels of pretranslational message for cachectin (messenger RNA) in a burn and infection rodent model. Adult Wistar rats were grouped as follows: (1) freely fed, (2) 30% burn, (3) 30% burn with Pseudomonas aeruginosa infection, (4) pair fed, and (5) 30% burn and infection with recombinant cachectin. Compared with controls or animals only burned, burned and infected rats had a 100% increase in hepatic cachectin messenger RNA content, lost carcass protein, and exhibited muscle loss with sparing of liver mass. Tissue production of cachectin as well as other cytokines may be sufficient to mediate several body composition changes observed in response to injury and infection.     

Flow cytometric measurement of rat lymphocyte subpopulations after burn injury and burn injury with infection

Increased infection rates in burned patients may result from a disproportionate increase in the suppressor subpopulations. Measurement of lymphocyte subpopulations is difficult in burned patients because gradient-purified cells are contaminated by nonlymphoid cells. The accuracy of flow cytometric subpopulation analysis was improved by restricting (gating) the analysis to cells with light-scatter intensity typical of lymphocytes. Blood was obtained 48 hours after burn from rats receiving no burns, 30% scald burns, or burns seeded with Pseudomonas aeruginosa to induce infection. Subpopulations were identified by monoclonal antibodies to T-lymphocyte antigens. Gating increased the values obtained for most subpopulations, but the relative differences between groups were unchanged. Burned and infected animals, but not animals burned only, had a decreased ratio of helper to suppressor lymphocytes (HSR) relative to control. A decreased HSR correlated with sepsis, but not with infection susceptibility. This suggests that a decrease in HSR may be a result of infection rather than a cause of susceptibility to infection.     

Bacterial translocation and its relationship to visceral blood flow, gut mucosal ornithine decarboxylase activity, and DNA in pigs

The relationship of bacterial translocation to gut blood flow and mucosal integrity was studied in pigs. Three groups of miniature pigs were studied: sham injured (controls) (n = 7), 50% mechanical reduction in blood flow to the superior mesenteric artery (SMA) and celiac artery (CA) (n = 6), and a 40% third-degree cutaneous flame burn (n = 9). Forty-eight hours after injury, animals were killed and organ samples obtained for analysis. Bacteria of the same biotype as that found in the intestinal lumen were present in the mesenteric lymph nodes (MLN) of 9 of 9 burned pigs and 5 of 6 pigs undergoing partial vascular occlusion. The DNA content and ornithine decarboxylase (ODC) activity were increased in the colon mucosa of animals from both the reduced-flow and burn-injured groups compared with control animals. Decreased blood flow to the gut may contribute to the development of bacterial translocation. In addition, intestinal regenerative capacity remains intact 48 hours after injury.     

Peripheral blood mononuclear cells exhibit hypercatabolic activity in response to thermal injury correlating with diminished MHC I expression

BACKGROUND: Muscle wasting is one of the major consequences of severe injury or infection. Although the mechanisms underlying this hypercatabolic state are not completely characterized, it was hypothesized that other cells in the body would be similarly affected. In particular, we sought to determine whether lymphoid cell populations experienced increased protein turnover after burn injury in a fashion analogous to that seen in skeletal muscle. METHODS: BALB/c mice received either a 20% total body surface area burn or a control sham treatment. At days 1, 2, and 7 after treatment, skeletal muscle, peripheral blood, spleen, and lymph nodes were harvested from both groups. Protein synthesis and degradation rates were measured using 14C-phenylalanine incorporation and tyrosine release. Lymphocyte subpopulations (CD4 and CD8 T cells, macrophages, and B cells) and expression of major histocompatibility complex I (MHC I) molecules were assessed by flow cytometry. RESULTS: The burn model used in this study resulted in increased skeletal muscle protein turnover in the first 2 days after injury. Protein synthetic and degradation rates of peripheral blood mononuclear cells (PBMNCs) in burned mice also demonstrated comparable changes, but persisted through day 7. Splenocytes showed similar hypercatabolic effects, whereas lymph node cells showed no change. Cell viability analysis confirmed that the observed alterations were not caused by cell death. MHC I expression was depressed in tandem with the increased catabolic rate in PBMNCs. CONCLUSION: This study demonstrates that various lymphoid populations undergo protein catabolic changes similar to those characteristically observed in skeletal muscle, and these correlated with diminished MHC I expression. Moreover, PBMNCs exhibited prolonged sensitivity to burn injury, of a duration exceeding that observed in skeletal muscles or other lymphoid tissues.     

Heparin-binding epidermal growth factor–like growth factor attenuates acute lung injury and multiorgan dysfunction after scald burn

Background

Impaired gut barrier function and acute lung injury (ALI) are significant components of the multiorgan dysfunction syndrome that accompanies severe burns. Heparin-binding epidermal growth factor–like growth factor (HB-EGF) has been shown to reduce inflammation, preserve gut barrier function, and protect the lungs from acute injury in several models of intestinal injury; however, comparable effects of HB-EGF after burn injury have never been investigated. The present studies were based on the hypothesis that HB-EGF would reduce the severity of ALI and multiorgan dysfunction after scald burns in mice.

Materials and methods

Mice were randomized to sham, burn (25% of total body surface area with full thickness dorsal scald), and burn + HB-EGF groups. The HB-EGF group was pretreated with two enteral doses of HB-EGF (1200 μg/kg/dose). Mice were resuscitated after injury and sacrificed at 8 h later. Their lungs were harvested for determination of pulmonary myeloperoxidase activity, wet:dry ratios, and terminal deoxynucleotidyl transferase dUTP nick end label and cleaved caspase 3 immunohistochemistry. Lung function was assessed using the SCIREQ Flexivent. Splenic apoptosis was quantified by Western blot for cleaved caspase 3, and intestinal permeability was measured using the everted gut sac method.

Results

Mice subjected to scald burn injury had increased lung myeloperoxidase levels, increased pulmonary and splenic apoptosis, elevated airway resistance and bronchial reactivity, and increased intestinal permeability compared with sham mice. These abnormalities were significantly attenuated in mice that were subjected to scald burn injury but treated with enteral HB-EGF.

Conclusions

These data suggest that HB-EGF protects mice from ALI after scald burn and attenuates the severity of postburn multiorgan dysfunction.     

组蛋白去乙酰化酶抑制剂对50％总体表面积烫伤大鼠存活率和脏器功能的影响

目的：研究组蛋白去乙酰化酶抑制剂对无液体复苏时致死性烫伤休克大鼠存活率和脏器功能的改善作用.方法：64只SD雄性大鼠随机分为4组：假烫组（n=10）,烫伤组（n=18）,烫伤＋2-甲基-2-乙酸组（2M2P组,n=18）和烫伤＋丙戊酸钠组（VPANa组,n=18）.烫伤组于80 ℃水浴浸泡背部15 s、双下肢15 s、腹部8 s,造成50%TBSAⅢ度烫伤.假烫组于37 ℃水浴浸泡,部位和时间与烫伤组相同. 2M2P组和VPANa组致伤方法同烫伤组,并于烫伤后即刻皮下注射2M2P或VPANa 300 mg/kg.各组大鼠烫伤深度经组织病理证实,于伤后2h和6h取腹主动脉血检测血清丙氨酸转氨酶（ALT）、肌酐（Cr）和肌酸激酶同工酶（CK-MB）等脏器功能指标.另66只大鼠随机分为烫伤组（n=18）、2M2P组（n=24）和VPANa组（n=24）,观察其伤后6 h和12 h生存率.结果：VPANa组生存时间为（776.7±89.5）min,显著高于烫伤组[（360.8±27.4）min]和 2M2P组[（512.5±52.2）min],差异具有显著性（P＜0.05）.VPANa组伤后6 h和12 h生存率分别为83.3%和50.0%,显著高于烫伤组（50.0%和0）和2M2P组（66.7%和16.7%）,差异具有显著性（P＜0.05）;2M2P组6 h和12 h生存率也显著高于烫伤组（P＜0.05）.烫伤及烫伤后各处理组伤后2 h和6 h ALT、Cr和CK-MB均显著高于假烫组（P＜0.05）.伤后6 h VPANa组ALT、Cr和CK-MB显著低于烫伤组和2M2P组（P均＜0.05）,2M2P组虽低于烫伤组,但差别无统计学意义.结论：组蛋白去乙酰化酶抑制剂能显著改善致死性烫伤休克大鼠脏器功能指标,延长动物生存时间.丙戊酸钠作用明显强于2M2P,有希望成为战场或灾害现场无液体复苏条件下救治致死性烧伤休克的潜力药物.     

Burn injury and pulmonary sepsis: development of a clinically relevant model

BACKGROUND: Despite improvements in the early resuscitation of the critically injured, mortality from multiple organ failure has remained stable, with the lung often the first organ to fail. Early intubation and mechanical ventilation predispose patients to the development of pneumonia and respiratory failure. Our objective was to establish a murine model of combined injury, consisting of burn/trauma and pulmonary sepsis with reproducible end-organ responses and mortality. METHODS: Male B6D2F1 mice were divided into four groups: burn/infection (BI), burn (B), infection (I), and sham (S). Burned animals had a full-thickness 15% dorsal scald burn. BI and I groups were inoculated intratracheally with Pseudomonas aeruginosa (3-5 x 103 colony-forming units). S and B animals received saline intratracheally. All animals were resuscitated with 2 mL of intraperitoneal saline. Mortality was recorded at 24, 48, and 72 hours. Bacterial sepsis was confirmed by tissue Gram's stain of the lungs and positive organ and blood cultures for Pseudomonas aeruginosa. Femoral bone marrow cells were collected at 72 hours from surviving animals. Clonogenic potential was assessed by response to macrophage (M) colony-stimulating factor (CSF) and granulocyte-macrophage (GM) CSF in a soft agar assay and the data were represented as colonies per femur. Isolated alveolar macrophages and whole lung tissue were assayed for levels of the inflammatory cytokines tumor necrosis factor-alpha and interleukin-6. RESULTS: Mortality at 72 hours was 30% in BI, 12% in I, and <10% in B and S groups. Pneumonia was documented in all infected animals at 24 hours by Gram's stain and positive tissue cultures for Pseudomonas aeruginosa. Systemic sepsis as confirmed by blood, and remote organ cultures was seen in BI animals only. Significantly increased responsiveness to M-CSF stimulations was noted in all groups (BI, 8,291 +/- 1,402 colonies/femur; B, 6,357 +/- 806 colonies/femur; and I, 8,054 +/- 1,112 colonies/femur; p < 0.05) relative to sham (3,369 +/- 883 colonies/femur, p < 0.05). Maximal responsiveness to GM-CSF stimulation was noted in the BI group (11,932 +/- 982 colonies/femur, p < 0.05), and similar GM responsiveness was noted in all other groups (B, 7,135 +/- 548 colonies/femur; I, 7,023 +/- 810 colonies/femur; and S, 6,829 +/- 1,439 colonies/femur). Alveolar macrophage release of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-6 increased in all animals, but the magnitude of increase was not proportional to the strength of the inciting stimulus. CONCLUSION: Although minimal perturbations were seen after burn or pulmonary infection alone, the combined insult of burn and pulmonary sepsis resulted in statistically significant hematopoietic changes with increased monocytopoiesis. Only the combined injury resulted in systemic sepsis and significantly increased mortality. We have developed a clinically relevant model of trauma and pulmonary sepsis that will allow further clarification of the inflammatory response after injury and infection.     

Lymphoid subpopulation changes after thermal injury and thermal injury with infection in an experimental model.

Subpopulation analysis of peripheral blood lymphocytes is a frequently used measure of immunocompetence. Yet, little is known about the lymphocyte subpopulations in the circulation and lymphoid organs after severe trauma. Blood, spleen, and lymph node (LN) subpopulations were compared in a rat model of burn injury (B) and burn injury with infection (BI). B and BI rats received 30% total body surface scald burns. Infection was induced by seeding wounds with Pseudomonas aeruginosa. Subpopulations were identified by flow cytometry 48 hours after burn. Helper lymphocytes were selectively depleted from the circulation of BI but not B animals, which caused the ratio of helper to suppressor cells (HSR) in BI animals to decrease significantly compared with the unburned controls. Both LN helper and suppressor cells were decreased in BI animals and the HSR was unchanged, but a selective reduction in suppressor cells in B LN increased the HSR relative to unburned controls. Spleen subpopulations were unchanged for both B and BI groups. Subpopulation changes after trauma and infection were different for each tissue examined.     

Cold-water treatment of scald injury and inhibition of histamine-mediated burn edema

Using the hairless mouse ear burn model we have studied the effects of immediate short-term cold-water treatment (CWT) of a moderate scald injury (54°C water for 20 sec) to intact skin using 8–10°C water for 5 min. CWT following scald injury caused brief periods of arteriolar vasomotion and shortened the duration of postburn venular dilation by about 50% as compared to untreated burns. CWT significantly (P < 0.05) reduced edema formation of the burned ear for only the first 2 hr after injury as compared to untreated burns. Significant delayed remote edema formation normally observed in abdominal and unburned (contralateral) ear skin after untreated ear scald injury was abolished after CWT to the burned ear. Chemical inhibition of remote burn edema, comparable to that achieved with CWT, was produced by cimetidine pretreatment or histamine depletion prior to injury. CWT also significantly decreased tissue histamine loss of the burned ear after scald injury Ultrastructural demonstration of increased vacuole formations in capillary and venular endothelial cells in edematous, unburned ear skin 2 hr after untreated scald injury suggested the presence of histamine-mediated remote burn edema formation. Predominant pathophysiologic mechanisms of CWT in local and remote burn edema inhibition and perhaps burn shock protection were suggested as: (1) decreased vascular response with a shortened duration of postburn venular dilation, and, most importantly, (2) the inhibition of local and systemic histamine release from thermally injured tissues.     

早期手术对烧伤大鼠肝血流量的影响

目的通过测定 TBSA30％Ⅲ度烧伤大鼠早期手术后肝血流量的变化,了解早期手术对肝脏血液灌流的影响。方法 Wistar 雄性大鼠34只,分为4组:烧伤组(A 组),输液组(B 组),早期手术组(C 组),正常对照组(D 组)。输液组经股静脉插管输入乳酸林格氏液;早期手术组于立即补液的同时行切痂同种异体植皮术。各组于伤后0,0.5,1,2,3,6,12和24小时,应用氢清除法测定肝血流量。结果 A 组与 B 组伤后均出现肝血流量显著下降,B 组直至伤后24小时肝血流量才恢复正常,而 C 组伤后肝血流量保持相对稳定,与正常对照组比较无显著意义。结论严重烧伤后立即液体复苏尚不足以维持有效的肝脏血流灌流,烧伤后早期手术尽早地去除焦痂组织,对改善肝血流量具有重要作用。     

Effect of early wound excision on changes in plasma nitric oxide and endothelin-1 level after burn injury: an experimental study in rats

The purpose of this study was to evaluate effects of early wound excision on changes in NO and endothelin-1 (ET-1) level in the plasma after extensive burn injury. The effects on vascular permeability and hepatic blood flow (HBF) were also assessed. Male Wistar rats were used for this study. A 30% total body surface area (TBSA) third-degree burn was made on the back. Then animals were divided into four groups. Burn group (n = 13), burn alone; infusion group (n = 13), burn injury and fluid resuscitation; early excision group (n = 13), burn injury, total wound excision at 30 min after the injury followed with immediate allogenic skin graft and fluid resuscitation; and the sham group (n = 15). The sham group and the early excision group did not show significant changes in the NO and ET-1 level in plasma during experimental period, while the burn group and the infusion group showed significant increase in the NO and ET-1. The early excision group also did not show hypovolemia, and the significant decrease in the HBF. These data suggest that the increased NO and ET-1 in plasma following thermal injury were originated from burned tissue and the removal of these injured tissue has beneficial effect on the vascular permeability and the changes in HBF.     

严重烫伤大鼠早期心肌抑制对肝肾肠损害的影响

目的 了解严重烫伤大鼠早期心肌抑制对肝、肾、肠损害及血流灌注的影响.方法 将32只Wistar大鼠按随机数字表分为假伤组、普萘洛尔组、烫伤对照组和烫伤+普萘洛尔组,每组8只.各组大鼠腹腔注射10 g/L戊巴比妥钠(30 mg/kg)麻醉后,假伤组、普萘洛尔组置于37℃水中18 s致假伤,其余2组置于97℃水浴中18 s,造成30%TBSAⅢ度烫伤.伤后30 min按Parkland公式腹腔注射复方乳酸钠林格液(4 mL·kg-1·1%TBSA-1).普萘洛尔组、烫伤+普萘洛尔组补液的同时静脉注射普萘洛尔0.75 mg/kg.伤后6 h以多道生理信号采集仪检测大鼠动脉收缩压(SBP)、动脉舒张压(DBP)、平均动脉压(MAP)以及左心室收缩压(LVSP)、左心室舒张末期压(LVEDP)、左心室压力最大上升/下降速率(±dp/dt max);以激光多普勒血流仪检测肝、肾、肠血流量;同时抽取大鼠静脉血检测血清心肌肌钙蛋白I(cTnI)、总胆汁酸(TBA)、β2-微球蛋白(β2-MG)浓度和二胺氧化酶(DAO)活性.结果 普萘洛尔组除LVEDP外,SBP、DBP、MAP、LVSP、±dp/dt max均低于假伤组(P<0.05).烫伤对照组与假伤组比较,心肌力学指标均下降(P<0.05).烫伤+普萘洛尔组与烫伤对照组比较,各项心肌力学指标均明显下降(P<0.05).与假伤组比较,烫伤对照组肝、肾、肠血流量显著降低(P<0.05);与烫伤对照组比较,烫伤+普萘洛尔组肝、肾、肠血流量降低(P<0.05).烫伤对照组血清cTnI、TBA、β2-MG和DAO值分别为(4.86±0.29)μg/L、(83.6±18.2)μmol/L、(2.75±0.19)mg/L、(1.45±0.09)×103U/L,均高于假伤组[(1.73±0.09)μg/L、(24±2.4)μmol/L、(1.15±0.18)mg/L、(0.87±0.13)×103U/L,P<0.05];与烫伤对照组比较,烫伤+普萘洛尔组血清cTnI(5.95±0.42)μg/L、TBA(125.8±21.3)μmol/L、β2-MG(3.25±0.17)mg/L、DAO(1.83±0.13)×103U/L均明显升高(P<0.05).结论 严重烫伤大鼠早期心肌抑制能加剧肝、肾、肠损害,提示"休克心"可能是严重烧伤后早期肝、肾、肠血流量减少和损害的启动因素之一.     

Effects of interleukin-1alpha administration on intestinal ischemia and reperfusion injury,mucosal permeability,and bacterial translocation in burn and sepsis

OBJECTIVE: To evaluate the effect of interleukin-1alpha (IL-1alpha) on the mesenteric circulation, intestinal mucosal integrity, and bacterial translocation in a burn/endotoxemia chronic porcine model. SUMMARY BACKGROUND DATA: Major burn and sepsis are associated with a high mortality, ischemia/reperfusion injury to the intestine, and an increased rate of bacterial translocation. Pathologic alterations of IL-1 synthesis, degradation, and binding to receptors have been reported. Manipulation of IL-1-mediated effects might be of therapeutic utility. METHODS: Twenty-one female pigs were instrumented with an ultrasonic flow probe on the superior mesenteric artery and a catheter into the superior mesenteric vein. After 5 days, all animals were anesthetized, and 14 received 40% total body surface area third-degree burn. IL-1alpha was administered intravenously at 1,000 ng/kg to seven pigs immediately after burn. Eighteen hours after burn, 100 microg/kg lipopolysaccharide (LPS) was administered intravenously. Systemic and splanchnic hemodynamics were measured and blood samples were drawn for blood gas analysis. Intestinal permeability was assessed every 6 hours by measuring the lactulose/mannitol (L/M) excretion ratio. At the end of the study (42 hours), tissue samples were harvested for bacteriologic cultures. RESULTS: Mesenteric blood flow was significantly decreased after burn and endotoxin. Administration of IL-1alpha significantly improved mesenteric blood flow postburn and post-LPS. Mesenteric oxygen supply and consumption showed a significant reduction after burn. In contrast, animals treated with IL-1alpha showed an increase in postburn mesenteric oxygen supply and consumption. LPS-induced mesenteric hypoxia was also ameliorated by IL-1alpha treatment. Intestinal permeability, as assessed by the L/M ratio, showed a 7- and 10-fold elevation after thermal injury and LPS, respectively. In contrast, IL-1alpha-treated animals showed an increase of only three- and fourfold in the L/M ratio, respectively. Bacterial translocation was significantly increased in the burn/endotoxin group. IL-1alpha significantly reduced the rates of bacterial translocation. CONCLUSIONS: IL-1alpha treatment attenuates mesenteric ischemia and reperfusion injury induced by thermal injury and endotoxemia by improving mesenteric blood flow and oxygenation. Subsequently, IL-1alpha reduces intestinal permeability and bacterial translocation after burn and sepsis.