Intra-abdominal Sepsis In Rats Research Articles

Effect of celecoxib on intra-abdominal sepsis-induced lung injury in rats

Objectives: This experimental study investigated the preventive effects of Celecoxib, a selective COX-2 inhibitor, on lung injury induced by intra-abdominal sepsis in rats. The study assessed Celecoxib's potential to mitigate the harmful impacts of sepsis on lung tissue. Methods: Thirty male Wistar albino rats, divided into three groups: a normal control group, a sepsis-induced group treated with saline, and a sepsis-induced group treated with Celecoxib. Sepsis was induced using fecal intraperitoneal injection (FIP), followed by a one-hour administration of Celecoxib at 50 mg/kg/day to the treatment group. Biochemical analysis of lung tissue measured oxidative stress markers (malondialdehyde [MDA]) and pro-inflammatory cytokines (Tumor Necrosis Faftor-α [TNF-α]). Histopathological examination evaluated lung tissue damage, encompassing alveolar congestion, hemorrhage, inflammatory cell aggregation, and edema. Arterial blood gas analysis quantified partial oxygen (PaO2) and carbon dioxide (PaCO2) pressures. Results: Celecoxib-treated rats exhibited reduced oxidative stress markers with lower MDA levels, indicating decreased oxidative damage in lung tissue. Moreover, TNF-α and other pro-inflammatory cytokines were significantly reduced in lung tissues of Celecoxib-treated rats, indicating its anti-inflammatory effects. Histopathological examination revealed reduced lung tissue damage in Celecoxib-treated rats, including alveolar congestion, hemorrhage, and inflammatory cell aggregation. Arterial blood gas analysis showed improved oxygenation (PaO2) in the Celecoxib-treated group compared to untreated sepsis rats. Conclusions: Celecoxib demonstrated preventive effects against sepsis-induced lung injury in rats by mitigating oxidative stress and inflammation, thereby preserving lung tissue integrity—further research, including clinical trials, to validate its effectiveness and safety in human sepsis management.

Sulfasalazine prevents lung injury due to intra-abdominal sepsis in rats: possible role of Nrf2 and angiopoietin-2

This study aimed to investigate the effect of sulfasalazine in preventing and treating intra-abdominal sepsis-induced acute respiratory distress syndrome (ARDS) in a rat model. Forty male Wistar albino rats were used. The rats were randomly divided into four equal groups, and sepsis was induced in 30 rats by intraperitoneal administration of a fecal saline solution prepared from rat feces. Group 1: normal control (n=10) [non-surgical], Group 2: fecal intraperitoneal injection (FIP) (n=10) [untreated septic group], Group 3: FIP+saline (placebo) (n=10) [saline administered intraperitoneally], Group 4 (n=10): FIP+sulfasalazine [250 mg/kg per day administered intraperitoneally]. Computed tomography was performed and blood samples were collected for biochemical and blood gas analysis. The lungs were removed for histopathological studies. Statistically significant reductions in interleukin (IL)-6, IL1-β, tumor necrosis factor (TNF)-α, malondialdehyde (MDA), and angiopoietin-2 (ANG-2) levels were observed in the sulfasalazine group compared to the FIP+saline group (P<0.001). Nrf2 levels were significantly higher in the sulfasalazine-treated group than in the FIP and FIP+saline groups (P<0.01). Lung tissue scores were significantly reduced in the sulfasalazine group compared to the other sepsis groups. The Hounsfield unit (HU) value was significantly lower in the sulfasalazine group than in the FIP+saline group (P<0.001). PaO2 values were significantly higher in the sulfasalazine-treated group than in the FIP+saline-treated group (P<0.05). Sulfasalazine was shown to be effective in preventing and treating ARDS.

Propofol increases morbidity and mortality in a rat model of sepsis.

IntroductionSevere sepsis is associated with approximately 50% mortality and accounts for tremendous healthcare costs. Most patients require ventilatory support and propofol is commonly used to sedate mechanically ventilated patients. Volatile anesthetics have been shown to attenuate inflammation in a variety of different settings. We therefore hypothesized that volatile anesthetic agents may offer beneficial immunomodulatory effects during the course of long-term intra-abdominal sepsis in rats under continuous sedation and ventilation for up to 24 hours.MethodsSham operation or cecal ligation and puncture (CLP) was performed in adult male Wistar rats followed by mechanical ventilation. Animals were sedated for 24 hours with propofol (7 to 20 mg/kg/h), sevoflurane, desflurane or isoflurane (0.7 minimal alveolar concentration each).ResultsSeptic animals sedated with propofol showed a mean survival time of 12 hours, whereas >56% of all animals in the volatile groups survived 24 hours (P <0.001). After 18 hours, base excess in propofol + CLP animals (−20.6 ± 2.0) was lower than in the volatile groups (isoflurane + CLP: -11.7 ± 4.2, sevoflurane + CLP: -11.8 ± 3.5, desflurane + CLP -14.2 ± 3.7; all P <0.03). Plasma endotoxin levels reached 2-fold higher levels in propofol + CLP compared to isoflurane + CLP animals at 12 hours (P <0.001). Also blood levels of inflammatory mediators (tumor necrosis factor-α, interleukin-1β, interleukin-10, CXCL-2, interferon-γ and high mobility group protein-1) were accentuated in propofol + CLP rats compared to the isoflurane + CLP group at the same time point (P <0.04).ConclusionsThis is the first study to assess prolonged effects of sepsis and long-term application of volatile sedatives compared to propofol on survival, cardiovascular, inflammatory and end organ parameters. Results indicate that volatile anesthetics dramatically improved survival and attenuate systemic inflammation as compared to propofol. The main mechanism responsible for adverse propofol effects could be an enhanced plasma endotoxin concentration, leading to profound hypotension, which was unresponsive to fluid resuscitation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0751-x) contains supplementary material, which is available to authorized users.

The effects of β-glucan on iron levels and lipid peroxidation in intra-abdominal sepsis in rats

Sepsis is defined as a systemic response of organisms to microorganisms and toxins. Sepsis is associated with the enhanced generation of reactive oxygen metabolites, leading to multiple organ dysfunctions. β-glucan is accepted to be one of the most powerful immune response modifiers. The aim of this study was to investigate the putative protective effect of β-glucan on changes of iron and malondialdehyde (MDA) levels in various tissue and blood after experimental sepsis in rats. Sepsis was induced by cecal ligation and perforation (CLP) in 32 male Wistar albino rat. To evaluate this, rats were divided into four groups as sham operated, β-glucan treated sham operated, CLP and β-glucan treated CLP. Sixteen hours after operation, rats were decapitated and MDA and iron levels were measured in the liver, kidney, heart, diaphragm tissues and blood. Also, whole tissue histopathology was evaluated by a light microscope. The results demonstrate that sepsis significantly decreased iron levels of all tissues and blood. The decrease in tissue iron levels and the increase MDA levels demonstrate the role of trace elements and free radicals in sepsis-induced tissue damage. Our results indicate that the given dose of β-glucan was probably insufficient to prevent sepsis-induced organ injury.

Magnolol alters cytokine response after hemorrhagic shock and increases survival in subsequent intraabdominal sepsis in rats.

Magnolol is a Chinese herb that has potent antioxidant effects. This study evaluated the effect of magnolol in the treatment of severe injury using a two-hit model in Sprague-Dawley rats. Hemorrhagic shock followed by resuscitation was performed. Intra-abdominal sepsis was induced by cecal ligation puncture. The rats were randomly segregated into the following three groups: group 1 (sham group) rats were sham-operated; group 2 (untreated group) rats received hemorrhagic shock and resuscitation and cecal ligation puncture 24 h later; and group 3 (treated group) rats were treated with magnolol and subjected to the same procedures as group 2. Plasma cytokine levels and tissue cytokine contents of lung, including tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-10 were assayed after hemorrhagic shock and sepsis. Pulmonary injury study was performed using Evans blue dye and survival analysis was performed after development of sepsis. Plasma and tissue TNFalpha levels increased after hemorrhagic shock. Magnolol treatment blunted the TNFalpha levels in plasma and tissue. The plasma IL-10 level increased after hemorrhagic shock, whereas the tissue level of IL-10 did not change. Magnolol treatment did not alter the plasma level of IL-10 but did increase tissue level. After sepsis, TNFalpha levels in both plasma and tissue of magnolol-treated animals were significantly lower than those in untreated animals, whereas plasma and tissue IL-10 levels were not significantly different between treated and untreated groups. Pulmonary injury study showed that magnolol-treated rats had decreased pulmonary permeability after the onset of sepsis. Survival analysis showed that survival rate was significantly higher in the treated group. In conclusion, magnolol modifies the cytokine response after hemorrhagic shock and resuscitation; the proinflammatory cytokine response is suppressed. The modified cytokines response induced by magnolol may result in decreased tissue injury and increased survival in subsequent intra-abdominal sepsis.

Comparative efficacy of BMS-284756, a new fluoroquinolone, versus established antimicrobial regimens for the treatment of experimental intra-abdominal sepsis in rats

Background: BMS-284756 is a new des-fluoro-(6)-quinolone with broad anti-microbial activity against gram-negative and gram-positive facultative and obligately anaerobic bacteria, including certain quinolone-resistant organisms. Objective: The purpose of this animal study was to examine the efficacy of BMS-284756 in a rat model of intra-abdominal sepsis. Methods: Five groups of 20 rats each were implanted with a gelatin capsule containing a mixed aerobe/anaerobe inoculum derived from the cecal contents of meat-fed rats. The inoculum was quantitatively and qualitatively examined to ensure that appropriate microbial species were present. Group 1 served as saline-treated controls; Group 2 received BMS-284756, 4 mg/d; Group 3 received BMS-284756, 9 mg/d; Group 4 received ampicillin plus sulbactam 77 mg TID; and Group 5 received a combination of gentamicin 2 mg TID plus clindamycin 15 mg TID. Dosage was determined for all antimicrobial agents based on peak and trough serum levels observed in previous tests, adjusting animal dosages according to a body surface area/body weight ratio and comparing these doses and levels to those from studies in humans. The end points were mortality during the first 2 to 4 days after initiation of sepsis and incidence of intraabdominal abscesses noted at necropsy. Results: The mortality rate was 65% in the control group versus 0% in the treatment groups ( P < 0.001). The incidence of abscess in survivors was 100% in the control group versus 10%, 10%, 5%, and 15% in Groups 2, 3, 4, and 5, respectively ( P < 0.001 vs control), with no significant differences between treatment groups. Conclusions: BMS-284756 is as effective as other established therapeutic regimens in reducing both mortality and the incidence of intra-abdominal abscesses in this animal model. These data suggest that BMS-284756 is an effective treatment for mixed intra-abdominal infections that involve both obligate anaerobes and facultative bacterial species.

Heparin reduces hepatic microperfusion damage during intraabdominal sepsis in rats

Heparin reduces hepatic microperfusion damage during intraabdominal sepsis in rats

Heparin reduces hepatic microperfusion damage during intraabdominal sepsis in rats

Heparin reduces hepatic microperfusion damage during intraabdominal sepsis in rats

Effect of early postoperative feeding on the healing of colonic anastomoses in the presence of intra-abdominal sepsis in rats.

Intra-abdominal infection is generally considered a major risk factor for dehiscence of primary colon anastomosis. To elucidate the indications for nutritional support during intra-abdominal sepsis, we investigated the healing of anastomoses in an animal model. Twenty male Sprague-Dawley rats (280-320 g) underwent cecal ligation and single puncture. After 24 hours the perforated cecum was removed, and the left colon was transected and anastomosed in a single-layer inverted fashion. Animals were randomly assigned to receive both chow and water (early-fed group; n = 10) or water alone for the first 72 hours and chow thereafter (late-fed group; n = 10). Colon-bursting pressure was measured five days after the anastomosis, at which time the anastomosis was excised. The survival rate after cecal ligation and single puncture was 100 percent, and blood cultures were positive in 20 percent of animals five days after surgery. All data are expressed as means +/- standard error of the mean. Body weight increased more in the early-fed group than in the late-fed group (15.6+/-3 vs. -6.3+/-2.8 g; P < 0.001). Early feeding resulted in increased anastomotic bursting pressure (200+/-11 vs. 161+/-12 mmHg; P < 0.05) and total collagen concentration at the site of anastomosis (2.36+/-0.09 vs. 2.01+/-0.07 microg/mg wet tissue; P < 0.01) compared with the late-fed group. Early feeding has a positive effect on anastomotic healing in the presence of intraabdominal sepsis. The mechanism by which early feeding enhances the colonic anastomotic healing is unclear, although preservation of colonic collagen seems to play a significant role.

Granulocyte colony-stimulating factor improves survival rate and reduces concentrations of bacteria, endotoxin, tumor necrosis factor, and endothelin-1 in fulminant intra-abdominal sepsis in rats

To study the therapeutic effect of granulocyte colony-stimulating factor (G-CSF) on the mortality rate and host defense pattern in fulminant intra-abdominal sepsis. Prospective, randomized, controlled trial. Research laboratory in a university hospital. Adult male Wistar rats. Fulminant polymicrobial intra-abdominal sepsis was induced by a 4-mm cecal perforation. Survival experiments were performed with two different doses of G-CSF (20 and 100 microg/kg/24 hrs), and therapy was started 7 days or 1 day before, or 4 hrs after sepsis induction (n = 24). To examine alterations in host response pattern, G-CSF (20 microg/kg/24 hrs) was given at sepsis induction, and rats were killed 4, 8, 12 and 24 hrs later (n = 8-16 per time period). Histologic examination of lung, liver, spleen, and kidney was performed, and blood concentrations of bacteria, endotoxin, tumor necrosis factor (TNF), endothelin-1, packed cell volume, and lactate were determined. G-CSF (20 microg/kg/24 hrs), given 4 hrs after sepsis induction, reduced the mortality rate from 96% to 42%. Increasing the dose (100 micrograms/kg/24 hrs), or giving G-CSF as prophylaxis (starting 7 days or 1 day before sepsis), gave no further protection. G-CSF attenuated the sepsis-induced enhancement of circulating bacteria, endotoxin, TNF, and endothelin-1, resulting in improved fluid balance and reduced lactate concentration. No histopathologic alterations were observed after G-CSF treatment. G-CSF improves host defense and survival rate in experimentally induced fulminant intra-abdominal sepsis. Clearance of bacteria and endotoxin is improved, concentrations of TNF and endothelin-1 are suppressed, and microvascular flow is improved. G-CSF does not induce neutrophil-mediated tissue damage.

Effect of volume support, antibiotic therapy, and monoclonal antiendotoxin antibodies on mortality rate and blood concentrations of endothelin and other mediators in fulminant intra-abdominal sepsis in rats

To study the therapeutic effects of volume support, antibiotics, and a monoclonal antiendotoxin antibody on the mortality rate and blood concentrations of endothelin and other mediators in fulminant intra-abdominal sepsis in rats. Prospective, randomized, controlled trial. Research laboratory in a university hospital. Adult male Wistar rats. Fulminant polymicrobial intra-abdominal sepsis was induced by a 4-mm cecal perforation. Treatment was performed with saline volume support, the antibiotic imipenem/cilastatin, and the monoclonal antiendotoxin antibody E5, both as monotherapy and as a combined regimen. Mortality rates were recorded and concentrations of bacteria, endotoxin, tumor necrosis factor (TNF), big endothelin, and endothelin-1 (21 amino acids) in blood were determined. Substantial increases in circulating big endothelin and endothelin-1 concentrations were observed during sepsis. The combination of volume support with antibiotics reduced the mortality rate, but neither as monotherapy nor as a combined regimen did this intervention modify plasma endothelin-1 concentrations. This finding suggests that hypovolemia and bacteria per se are not important stimuli for endothelin synthesis and a high plasma level of endothelin-1 does not necessarily predict poor outcome in sepsis. The inactive big endothelin is enzymatically cleaved, leaving the biologically active 21-residue endothelin-1. Intervention with E5 substantially reduced the mortality rate and concentrations of endotoxin, TNF, and plasma endothelin-1, while big endothelin and total endothelin immunoreactivity did not decrease. This finding indicates a suppressed conversion of big endothelin to endothelin-1 after E5 treatment. Because E5 has no direct effect on endothelin metabolism, E5 probably reduces the synthesis of endothelin-1 by suppressing the endothelin-activators endotoxin and TNF. A triple combination of volume support, imipenem/cilastatin, and E5 was the only regimen that reduced all of the end points: mortality rate, hemoconcentration, bacteria, endotoxin, TNF, and endothelin-1. The concentration of plasma endothelin was increased during fulminant intra-abdominal sepsis in rats. Combining volume support with antibiotic therapy reduced the mortality rate, but did not modify concentrations of plasma endothelin-1. The monoclonal antiendotoxin antibody E5 reduced the mortality rate and concentrations of endotoxin, TNF, and endothelin-1, but not big endothelin. This finding indicates that E5 therapy inhibits the conversion of big endothelin to 21-residue endothelin-1.

Synergistic Effect of E5, Imipenem, and Volume Support during Fulminant Intraabdominal Sepsis in Rats

The protective effect of volume support, imipenem, and the anti-endotoxin antibody E5 given as mono- or combination therapy was studied in fulminant intraabdominal sepsis in rats. Mortality, blood levels of bacteria, endotoxin, tumor necrosis factor (TNF), and lactate, and packed cell volume were measured. All monotherapy regimens improved survival, and protection decreased with delayed intervention. Volume support prevented dehydration and lactate accumulation but had no effect on levels of bacteria, endotoxin, or TNF. Imipenem killed bacteria and released endotoxin, and lactacidosis was reduced. E5 reduced endotoxin, TNF, and lactate but not bacteremia. The imipenem-induced increase in plasma endotoxin was abolished by E5. When E5 was added to a regimen of volume support plus imipenem 6 h after induction, it gave an extra improvement of survival, but this synergism disappeared when intervention was delayed 4 h more. The primary effect of E5 was a reduction in plasma endotoxin level.

Pentoxifylline improves survival and reduces tumor necrosis factor, interleukin-6, and endothelin-1 in fulminant intra-abdominal sepsis in rats.

The influence of pentoxifylline (PTX) on mortality and some important mediators was studied in a model of cecal perforation with fulminant intra-abdominal sepsis in rats. Cumulative mortality was registered in three groups of animals: untreated sepsis (n = 36), sepsis + PTX 20 mg/kg/24 h (n = 24), and sepsis + PTX 80 mg/kg/24 h (n = 24). PTX therapy was started at sepsis induction or after 4 h, and mortality was reduced from 89% in untreated sepsis to 60-66% in the PTX groups. Levels of sepsis mediators were studied in two groups: untreated sepsis and sepsis + PTX 40 mg/kg started 1 h after sepsis induction. In both groups 6-10 animals were sacrificed at 4 and 8 h to measure blood levels of bacteria, endotoxin, tumor necrosis factor (TNF), interleukin-6 (IL-6), endothelin-1, lactate, neutrophils, and packed cell volume. Cecal perforation gave high levels of bacteria, endotoxin, TNF, IL-6, and endothelin-1, leading to dehydration, lactacidosis, neutropenia, and death. Treatment with PTX did not modify dehydration, neutropenia, or concentrations of bacteria and endotoxin. Release of endothelin-1 was delayed, TNF burst was nearly abolished, and levels of IL-6 and lactate were substantially suppressed. In summary, PTX improves survival and reduces blood concentrations of TNF, IL-6, lactate, and endothelin-1 in fulminant intra-abdominal sepsis in rats. The primary effect of PTX in this sequence is probably reduction of TNF.

Effect of Intralipid on clearance and organ uptake of bacteria in intra-abdominal sepsis in rats

Although infusion of Intralipid ® has been reported to block reticuloendothelial system (RES) function, it is unclear if this is true at rates used clinically. This study investigates the effect of Intralipid ®, infused at a rate providing about half of the non-protein caloric needs, on survival and bacterial clearance in septic rats. Continuous infusion of Intralipid ® (0.9 g/100 g bw/d) or saline (controls) was started immediately after induction of hyperdynamic intra-abdominal sepsis (bacterial agents: E. coli, B. thetaiotamicron). RES function was studied by means of intravenous injection of Selenium-labelled, viable E. coli after 24 or 48 h. Compared to the saline-treated controls, Intralipid ® did not cause any change in clearance from blood or localisation to liver, spleen or lungs. The 24 and 48 h survival rates were about 80 and 65%, respectively, and similar in the two groups. It is concluded that infusion of Intralipid ® at a rate close to that used clinically did not impair survival or bacterial clearance in rats with gram-negative sepsis.

Peritonitis and intraabdominal abscess: An experimental model for the evaluation of human disease

An economical, reproducible experimental model of intraabdominal sepsis in rats has been developed. This model was produced by placing varying amounts of human fecal material within gelatin capsules, which were then surgically placed within the peritoneal cavities of rats. The type of intraabdominal sepsis produced varied according to the amount of inoculum introduced. The full spectrum of sepsis produced was similar to that seen in human peritonitis and intraabdominal abscess formation. This model is suitable for and is presently being used to evaluate the efficacy of the various antibiotic schemes currently used in the treatment of human intraperitoneal infections.

Therapy for Experimental Intraabdominal Sepsis: Comparison of Four Cephalosporins with Clindamycin Plus Gentamicin

An experimental model of intraabdominal sepsis in rats was used for evaluation of treatment with four cephalosporins: cephalothin, cefazolin, cefoxitin, and cefamandole. Doses were 115 mg of each of the cephalosporins/kg and, in additional experiments, 350 mg of cephalothin or cefazolin/kg. Response to treatment was evaluated by mortality rate and the incidence of intraabdominal abscess. All four cephalosporins and gentamicin produced a similar reduction in mortality rates. There was a marked variation in incidence of abscess dependent upon the cephalosporin selected and the dosage tested. Regimens most effective in reducing abscesses were clindamycin, low-dose cefoxitin, or high-dose cephalothin.