Hemorrhagic shock-induced bacterial translocation: the role of neutrophils and hydroxyl radicals

We previously documented a relationship between xanthine oxidase activation, intestinal injury, and bacterial translocation (BT) in rats subjected to hemorrhagic shock. The current experiments were performed to determine the relative roles of hydroxyl radicals and neutrophils in the pathogenesis of shock-induced mucosal injury and BT. The incidence of BT was higher in the shocked rats (30 mm Hg for 30 min) than the sham-shock controls (87% vs 12.5%; p less than 0.01). Administration of the hydroxyl radical scavenger, dimethyl sulfoxide (DMSO), or the iron chelator, deferoxamine, reduced the incidence of BT from 87% to 20% and 40%, respectively (p less than 0.05). DMSO and deferoxamine appear to prevent shock-induced BT by blunting the magnitude of shock-induced mucosal injury. In contrast, neutrophil depletion did not prevent BT or protect the intestinal mucosa in shocked rats. Instead, the incidence of systemic spread of translocating bacteria past the mesenteric lymph nodes to the livers and spleens of the shocked rats was higher in the neutrophil-depleted rats (56%) than in any other group (p less than 0.01). Thus, shock-induced BT and intestinal injury appear to be mediated by oxidants (.OH) derived from xanthine oxidase, rather than granulocytes.     

Endotoxin-induced bacterial translocation: a study of mechanisms

Previously, we documented that nonlethal doses of endotoxin cause the translocation (escape) of bacteria from the gut to systemic organs. The purpose of this study was to determine which portion(s) of the endotoxin molecule induces bacterial translocation and to examine the role of xanthine oxidase activity in the pathogenesis of endotoxin-induced bacterial translocation. Nonlethal doses of Salmonella endotoxin preparations (wild type, Ra, or Rb), containing the terminal portion of the core polysaccharide, induced bacterial translocation, whereas those preparations lacking the terminal-3 sugars (Rc, Rd, Re, or lipid A) did not induce bacterial translocation. Additionally, only those endotoxin preparations that induced bacterial translocation injured the gut mucosa, increased ileal xanthine dehydrogenase and oxidase activity, and disrupted the normal ecology of the gut flora, resulting in overgrowth with enteric bacilli. Inhibition of xanthine oxidase activity by allopurinol prevented endotoxin (Ra)-induced mucosal injury and reduced the incidence of bacterial translocation from 83% to 30% (p less than 0.01). These results suggest that endotoxin-induced bacterial translocation requires the presence of the terminal core lipopolysaccharide moiety and that xanthine oxidase-generated oxidants are important in the pathogenesis of endotoxin-induced mucosal injury and bacterial translocation.     

The protective role of ascorbic acid in burn-induced testicular damage in rats

Objective

To investigate the ability of ascorbic acid to protect the testes from damage in severe burns.

Design

Experimental study.

Setting

University of Lagos Medical School, Department of Anatomy.

Animals

28 adult male Wistar rats (250–300 g).

Intervention

Third degree burn was induced on 40% body surface area of rats and they were given ascorbic acid at 4 mg/kg over 8 weeks.

Main outcome measured

Weight of reproductive organs and epididymal sperm parameters were measured. Oxidative status was assayed and a semi-quantitative assessment of histologic changes was also carried out.

Results

Burn caused severe seminiferous tubular damage, especially germ cell loss (p < 0.05). This was matched by significant reduction in sperm density and morphology (p < 0.05). Burn also increased oxidative stress, with elevated malondialdehyde (MDA) levels (p < 0.01) and changes in catalase and superoxide dismutase enzyme levels. Ascorbic acid prevented the changes in all sperm parameters. It normalized MDA levels (p < 0.01) and attenuated changes in the levels of catalase and superoxide dismutase. Ascorbic acid treatment also significantly reduced histologic damage to seminiferous tubules.

Conclusion

This study shows that severe thermal injury causes significant testicular damage and impairs spermatogenesis. It also shows that ascorbic acid protects the testis from such damage and therefore has the potential to be a useful adjunct therapy during treatment of young males with severe burns.     

Abdominal radiation causes bacterial translocation

The purpose of this study was to determine if a single dose of radiation to the rat abdomen leads to bacterial translocation into the mesenteric lymph nodes (MLN). A second issue addressed was whether translocation correlates with anatomic damage to the mucosa. The radiated group (1100 cGy) which received anesthesia also was compared with a control group and a third group which received anesthesia alone but no abdominal radiation. Abdominal radiation lead to 100% positive cultures of MLN between 12 hr and 4 days postradiation. Bacterial translocation was almost nonexistent in the control and anesthesia group. Signs of inflammation and ulceration of the intestinal mucosa were not seen until Day 3 postradiation. Mucosal damage was maximal by Day 4. Bacterial translocation onto the MLN after a single dose of abdominal radiation was not apparently dependent on anatomical, histologic damage of the mucosa.     

Splenectomy influences endotoxin-induced bacterial translocation

To determine whether splenectomy affects the antibacterial defenses of the gut, experiments were performed using bacterial translocation (BT) as a marker of intestinal barrier failure. The incidence of BT was measured 8 days after splenectomy or sham-splenectomy in mice receiving or not receiving endotoxin (0.1 mg IP). Splenectomy does not appear to promote BT from the gut, since the incidence of bacterial translocation after splenectomy or sham-splenectomy (5%) were not different. A second experiment was performed to determine whether the resistance to endotoxin-induced BT was modified after splenectomy. The incidence of endotoxin-induced BT was 73% in the unoperated control group, 59% in the sham-splenectomy group, but 23% in the splenectomy group (p less than 0.002). Thus, splenectomy but not sham-splenectomy increased the resistance of otherwise healthy mice to endotoxin-induced BT.     

The role of thermal injury on intestinal bacterial translocation and the mitigating role of probiotics: A review of animal and human studies

IntroductionBurn patients represent a combination of nutritionally deplete and calorically demanding individuals who are susceptible to morbidity and mortality. A source of sepsis in thermal injury patients is the gastrointestinal tract with its interaction of normal and potentially pathogenic bacteria. The normal flora of the intestines maintains the equilibrium of the gut and prevents bacterial translocation (BT) through numerous mechanisms, all of which are disrupted as a consequence of thermal injury. Probiotic supplements with varying strains of bacteria have the potential to stabilize the integrity of the gut lining and decrease the incidence of BT after thermal injury.MethodsA literature review was conducted for animal and human studies in English addressing probiotic therapy in thermal injury. Keywords, “probiotics,” “thermal injury” and “burn” were utilized. Reference lists for each analyzed article were also examined to ensure completeness of literature search. Each article was reviewed for methodology, results and conclusions.ResultsEleven and six unique articles were identified addressing probiotics in thermal injury in animal and human studies, respectively. Heterogeneity between studies and limited demographic and outcome reporting prevented meta-analysis and comprehensive recommendations to be formalized.ConclusionWhile heterogeneity did not allow for meta-analysis, the results overall suggest a preventative, if not therapeutic, potential for probiotics in patients after thermal injury. Despite initial concern that probiotic therapy could lead to systemic infection in immune compromised individuals, this was not observed in the analyzed studies. Numerous unanswered questions exist in regards to optimizing probiotic therapy in patients after thermal injury.     

Immunosuppression and intestinal bacterial overgrowth synergistically promote bacterial translocation

Gram-negative, enteric bacilli of the indigenous gastrointestinal tract microflora translocated primarily to the mesenteric lymph nodes in mice given either oral penicillin G sodium or clindamycin hydrochloride. These bacteria also translocated to the mesenteric lymph nodes in mice injected with cyclophosphamide or prednisone. However, in mice treated with the combination of an oral antibiotic plus an immunosuppressive drug, the translocating bacteria spread systemically to the peritoneal cavity. When the treatment with clindamycin and prednisone was extended to 12 days, the mice died of lethal sepsis beginning eight days after treatment. Thus, the combination of intestinal bacterial overgrowth and host immunosuppression synergistically promoted bacterial translocation from the gastrointestinal tract that resulted in lethal sepsis.     

Causes of surgical sepsis including bacterial translocation

Sepsis is defined as the systemic inflammatory response syndrome (SIRS) associated with suspected or confirmed infection. As such, it is implicit that two components are necessary in the causation of surgical sepsis; namely a source of infection as well as a SIRS response by the patient. This article reviews some of the better known causes and predisposing factors for sepsis, including that of the passage of viable bacteria or its components across the gut barrier in a process known as bacterial translocation (BT). A particular emphasis is paid to the development of sepsis in surgical patients. The common infections encountered in surgical patients are also discussed together with the specific definitions used in relation to surgical site infections.