Rat Model Of Peritonitis Research Articles

Prevention of Intraperitoneal Adhesions and Abscesses by Polysaccharides Isolated From Phellinus spp in a Rat Peritonitis Model

To assess whether polysaccharides isolated from fungi, Phellinus spp, could reduce the adhesion and abscess formation in a rat peritonitis model. Although polysaccharides from Phellinus spp is a well-known material with antiinflammatory properties, little is known regarding its ability to prevent intraperitoneal adhesions. We have assessed the adhesion- and abscess-reducing effect of polysaccharides from Phellinus gilvus (PG) and Phellinus linteus (PL) in a rat peritonitis model. In 60 SD rats, experimental peritonitis was induced using the cecal ligation and puncture model (CLP). Animals were randomly assigned to 5 groups; ringer lactate solution (RL group), polysaccharides from PG and PL (PG and PL group), hyaluronic acid (HA group), and carboxymethylcellulose (CMC group). Intraperitoneal adhesions and abscesses were noted at 7 day after CLP. RT-PCR assay for urokinase-type plasminogen activator (uPA), its cellular receptor (uPAR), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), and tumor necrosis factor (TNF)- alpha was performed to assess the cecal tissue. Adhesion formation was significantly reduced in PG, PL, CMC, and HA groups (P < 0.001) compared with that in RL group. The incidence of abscesses was also significantly reduced in PG and PL groups (P < 0.05) compared with that in the RL group. The level of uPA, uPAR, tPA, and TNF-alpha was highly expressed in PG and PL group, as compared with the RL group. We concluded that PG and PL had significant adhesion- and abscess-reducing effects and may act by modulating fibrinolytic capacity of uPA and/or tPA produced from macrophages in a rat peritonitis model.

Comparison of intraperitoneal anti-adhesive polysaccharides derived fromPhellinusmushrooms in a rat peritonitis model

To assess the adhesion- and abscess-reducing capacities of various concentrations of polysaccharides derived from fungus, Phellinus gilvus (PG) or Phellinus linteus (PL) in a rat peritonitis model. In 96 SD rats, experimental peritonitis was induced using the cecal ligation and puncture model (CLP). Rats were randomly assigned to 8 groups; Ringer's lactate solution (RL group), hyaluronic acid (HA group), 0.025%, 0.25%, and 0.5% polysaccharides from PG (PG0.025, 0.25, and 0.5 groups), and PL (PL0.025, 0.25, and 0.5 groups). Adhesions and abscesses were noted at 7 d after CLP. RT-PCR assay was performed to assess the cecal tissue. Adhesion formation was significantly reduced in PG0.25, 0.5, PL0.25, 0.5, and HA groups (2.5+/-0.7, 2.4+/-0.7, 3.8+/-1.0, 3.6+/-0.8, and 2.7+/-1.1, P<0.05). The incidence of abscesses was significantly reduced in all treated groups compared to RL group (58%, P<0.05). The urokinase-type plasminogen activator (uPA) gene expression was greatly up-regulated by increasing the concentration of polysaccharides. The urokinase-type plasminogen activator receptor (uPAR) and tumor necrosis factor (TNF)-alpha mRNA were highly expressed in PG0.25, 0.5, PL0.25, and 0.5 groups. We concluded that 0.5% polysaccharide derived from PG and PL was the optimal concentration in preventing adhesion and abscess formation and may act by modulating activity of uPA and TNF-alpha in a rat peritonitis model.

Therapeutical and inflammatory response in rats with secondary peritonitis and topical use of ampicilin/sulbactam

The acute peritonitis is an important cause of sepsis and death on intensive care units and surgery. The treatment must include: systemical use of antibiotics, drainage of abscess and restauration of gastrointestinal integrity. The topical use of antibiotics in the peritoneal cavity is controversial. The aim of this study was to evaluate the use of topical use of ampicilin/ sulbactam in the treatment of peritonitis. We measured the plasmatic levels of nitric oxide, count of eosinophils, lymphocytes, monocytes, and neutrophils in blood and peritoneal cavity, using a model of peritonitis in rats (transfixation and ligature of cecum). Twenty four Wistar rats were divided in 4 groups (n = 6 each). group A: induction of peritonitis with ligature of cecum and topical treatment with saline; group B: induction of peritonitis with ligature of cecum and topical treatment with ampicilin/sulbactam; group C: transfixation of cecum; group D: laparotomy and peritoneal exsudate + blood sample. The transfixation-ligture of cecum remained for 24 hs before treatment. A relaparotomy was performed in 18 rats and peritoneal exsudate/blood were collected. Dosage of Nitric oxide, count of eosinophil, lymphocytes, monocytes, and neutrophils in blood and peritoneal exsudte were done. The difference was not significant in the levels of nitric oxide, eosinophil, lymphocytes, monocytes, and neutrophils in blood and peritoneal exsudate (p > 0,05) among the studied groups. The use of ampicilin associated to sulbactam via intraperitoneal in rats with fecal peritonitis did not change survival.; the levels of plama nitric oxide, count of eosinophil, lymphocytes, monocytes, and neutrophils in blood and peritoneal exsudate were not affected.

The Effect of Polysaccharides and Carboxymethylcellulose Combination to Prevent Intraperitoneal Adhesion and Abscess Formation in a Rat Peritonitis Model

Polysaccharides isolated from fungi, Phellinus spp. is well-known material with anti-tumor and anti-inflammatory properties. We have assessed the adhesion- and abscess-reducing capacity of carboxymethylcellulose (CMC) and polysaccharides from Phellinus spp. combination in a rat peritonitis model. In 72 Sprague-Dawley rats, experimental peritonitis was induced by means of the cecal ligation and puncture model (CLP). After 24 hr, the abdomen was reopened and the ligated cecum was resected. Peritoneal fluid samples were taken for microbiological examination. Rats were randomly assigned to 6 groups: ringer lactate solution (RL group), polysaccharides from Phellinus gilvus (PG group) and Phellinus linteus (PL group), carboxymethylcellulose (CMC group), and their combinations (PG+CMC and PL+CMC groups). Adhesions and abscesses were noted at day 7 after CLP. RT-PCR assay for urokinase-type plasminogen activator (uPA), its cellular receptor (uPAR), and tumor necrosis factor (TNF)-alpha was performed to assess the cecal tissue. Microbiological examination showed polymicrobial bacterial peritonitis. Adhesion formation was significantly reduced in PG+CMC and PL+CMC groups (P<0.05). The incidence of abscesses was reduced in all treated groups except the RL group (P<0.05). uPA, uPAR, and TNF-alpha mRNA were highly expressed in the PG+CMC and PL+CMC groups, as compared to the RL group. We concluded that the combination of polysaccharides and CMC had significant adhesion- and abscess-reducing effects compared with their single treatment and the effects may act by modifying the fibrinolytic capacity of uPA, uPAR and TNF-alpha produced from activated macrophages in a rat peritonitis model.

Fluconazole attenuates lung injury and mortality in a rat peritonitis model

Acute lung injury following peritonitis constitutes an enigmatic clinical problem with no specific therapy. Recently, immunomodulators such as azole compounds have been shown to attenuate shock-related tissue injury. The present investigation was undertaken to study the effect of fluconazole on acute lung injury and survival following faecal peritonitis in rats. Male Wistar rats weighing 225-235 g. Faecal peritonitis (Fp) was produced in four groups of adult male Wistar rats by intraperitoneal administration of non-sterile faecal suspension (1:1 w/v saline). A fifth group of rats was given sterile faecal material (SFM), which served as control. Rats in Fp groups were given fluconazole in doses of 0 mg/kg, 3 mg/kg, 10 mg/kg, and 30 mg/kg by gavage 30 min before induction of peritonitis. The control animals received an equal volume of distilled water. Survival over a period of 72 h, oxidative stress, neutrophil activity, and lung injury were measured. This study showed a 90% survival in the fluconazole-treated group compared to only 20% survival in untreated rats (P<0.008 log-rank test). The lungs of animals with Fp showed massive pathological changes including intraalveolar oedema, fibrosis, and mixed inflammatory cell infiltrate. These changes were dose-dependently attenuated by fluconazole. Enhanced oxidative stress (P<0.001) and neutrophil activity in the peritoneal fluid and lung (P<0.001) in Fp animals was dose-dependently reduced by fluconazole. This study clearly suggests the role of neutrophils in Fp-induced tissue injury/mortality, which may be dose-dependently, attenuated by fluconazole.

Activation of mast cells induced by agonists of proteinase-activated receptors under normal conditions and during acute inflammation in rats

Functions of thrombin as a modulator of inflammation and tissue repair are mediated by the proteinase-activated receptor (PAR) family. Some of these effects may be induced by activation of mast cells. To characterize the degranulation of rat peritoneal mast cells in response to PAR agonists, the effects of thrombin, trypsin and peptide agonists of PARs (PAR-AP, proteinase-activated receptor-activating peptides) on secretion were investigated. The release of β-hexosaminidase by thrombin (0.01–1 μM) was concentration-dependent and mediated via PAR 1, as evidenced by cathepsin G (100 μM)-induced inactivation of PAR 1 and thrombin-stimulated PAR 1 desensitization. Trypsin (1 μM) accelerated histamine secretion. The PAR 1-AP, TRAP (SFFLRN, 1–100 μM) and the PAR 2-AP SLIGRL (5–100 μM) caused the release of histamine, and β-hexosaminidase from inflammatory mast cells were obtained from a model of acute peritonitis in rats. Relative to the response to compound 48/80, the thrombin- and TRAP-induced release of β-hexosaminidase was higher in inflammatory mast cells than in the control. This suggests that additional exposure of PAR 1 on mast cells to PAR agonists or an increase in PARs sensitivity to PAR agonists probably occurred during acute inflammation.

Impact of elements containing glycopeptide resistance genes on expression of virulence in Enterococcus faecalis peritonitis: a pilot study with rats.

The relationship between virulence and chromosomal elements containing glycopeptide resistance genes was experimentally assessed for two transconjugant strains of Enterococcus faecalis (VanA and VanB phenotypes) and compared to that for a susceptible wild-type strain. Microbiologic and inflammatory effects were assessed in a polymicrobial rat model of peritonitis. Mean peritoneal enterococcus concentrations +/- standard deviations at day 1 were 2.1 +/- 1.9, 1.3 +/- 1.1, and 1.7 +/- 2.0 log(10) CFU/ml for susceptible, VanA, and VanB strains, respectively (P < 0.05). At day 3 also there were lower concentrations of glycopeptide-resistant enterococcal strains in peritoneal fluid (3.2 +/- 3.4, 1.8 +/- 1.8, and 2.1 +/- 2.4 log(10) CFU/ml for susceptible, VanA, and VanB strains, respectively [P < 0.05]). Transconjugant glycopeptide-resistant strains were associated with increased peritoneal cell counts at the different evaluation times of the experiment (P < 0.001). Plasma alpha1-acid glycoprotein concentrations were lower in the presence of the susceptible strain (667 +/- 189 mg/liter) than in the presence of the VanA or VanB strain (1,193 +/- 419 or 1,210 +/- 404 mg/liter, respectively [P < 0.05]), while concentrations of tumor necrosis factor alpha and interleukin-6 in peritoneal fluid remained similar for the strains. These results suggest a trend toward variation of virulence of transconjugant strains compared to the wild-type strain in this peritonitis model.

P-selectin blocking potency of multimeric tyrosine sulfates in vitro and in vivo

P-selectin blocking potency was investigated using synthetic monomeric and polymeric anionic compounds containing sulfate groups such as O-sulfotyrosine (sTyr) and/or sulfated Lewis structures. A non-carbohydrate-containing polyacrylamide conjugate sTyr–PAA (80% mol of sTyr) was a remarkably potent inhibitor of P-selectin binding in vitro, having an IC 50 value of 6 ng/mL (equivalent to 10 nM calculated on the basis of sTyr residues or 0.1 nM calculated by the mass of the macromolecule). The inhibitory effect of sTyr–PAA (80%) towards P-selectin is significantly greater than that of fucoidan (IC 50, 100 ng/mL). However, sTyr–PAA (80%) was less effective than fucoidan at reducing neutrophil extravasation in an in vivo rat model of peritonitis.

Cationic Peptides Combined with Betalactams Reduce Mortality from Peritonitis in Experimental Rat Model

The efficacy of cationic peptides combined with betalactams was investigated in a peritonitis rat model. Intraabdominal sepsis was induced in adult Wistar rats via cecal ligation and single puncture. The study included eight drug-treated groups: each of them received intravenous polymyxin-E (1 mg/kg), buforin II (1 mg/kg), imipenem (20 mg/kg), amoxicillin-clavulanate (50 mg/kg), polymyxin-E (1 mg/kg) plus imipenem (20 mg/kg), or amoxicillin-clavulanate (50 mg/kg), and buforin II (1 mg/kg) plus imipenem (20 mg/kg), or amoxicillin-clavulanate (50 mg/kg). The study included an untreated control group that received intravenous isotonic sodium chloride solution. All compounds significantly reduced the lethality and the number of bacteria in abdominal fluid compared with saline treatment. Among compounds, imipenem showed the highest antimicrobial activity, while buforin II produced the highest reduction in plasma endotoxin and TNF-α levels. Overall, buforin II and imipenem association were the most effective therapeutic approach. Data presented here suggest the potential advantages of combining antimicrobial agents and compounds able to neutralize the biological effect of the endotoxin.

Effect of L-NAME on decreased ileal muscle contractility induced by peritonitis in rats

Background/Purpose: It is now well established that intestinal inflammation is associated with disturbed contractility. The aim of this study was to determine the effects of peritonitis on longitudinal ileum smooth muscle responses to KCl, carbachol and substance P (SP) and to examine the role of nitric oxide (NO) and Nomega-nitro-L-arginine methylester (L-NAME) on ileal contractility in this peritonitis model. Methods: Peritonitis was induced by cecal ligation and puncture (CLP) in 20 rats. While 10 of these received 1 mL distilled water as placebo, the other 10 received 5 mg/kg (subcutaneously) L-NAME before the operation. Another group of 10 rats underwent a sham operation. Twenty-four hours after the operation, the rats were killed, and their ileum was excised. Ileum segments were placed in longitudinal direction in a 10-mL organ bath; concentration-response relationship for KCl, carbachol, and SP were obtained by adding the reagent cumulatively to the bath. Results: The KCl-, carbachol-, and SP-induced contractions were decreased markedly, with no change in the pD2 values in the peritonitis group compared with controls. Peritonitis-induced changes in the contractile responses were restored significantly by in vivo L-NAME pretreatment. Conclusions: The model of CLP-induced peritonitis in rats showed that KCl-induced nonreceptor-mediated, carbachol- and SP-induced receptor-mediated contractions are significantly decreased by inflammation in the longitudinal ileum muscle. Increased synthesis of NO may be responsible for these decreases in contractile responses because they were restored significantly by in vivo L-NAME injection. Inhibition of NOS with L-NAME injection may afford a new therapeutic approach to the treatment of gastrointestinal stasis in septic patients. J Pediatr Surg 37:901-905. Copyright 2002, Elsevier Science (USA). All rights reserved.

Optimal Timing and Temperature for Hyperthermic Preconditioning in an Animal Model of Fecal Peritonitis

The impact of immune parameters in the mechanism of hyperthermia is yet to be explained. In this study, the optimal timing and temperature of thermal treatment for reversing the abnormal immunologic parameters obtained in a rat model of peritonitis were planned to be determined. Male Sprague-Dawley rats were grouped as sham, control peritonitis, and thermally treated rats at the time of peritonitis or 4 h prior to induction of peritonitis both at 40 and 42°C. Peritonitis was induced by the cecal ligation and perforation model. Eight hours after the induction of peritonitis, rats were sacrified and samples were taken for measurements of CD 4 + , CD 8 + , CD 11b , B cells, NK cells, and tumor necrosis factor f (TNF f ) and thiobarbituric acid-reactive substances (TBARS) levels. CD 4 + expression and B cell amount were decreased whereas TNF f levels, CD 8 + and CD 11b expression, and NK cell amount were found to be increased in the control peritonitis group when compared to the sham group. Peritonitis induction also increased TBARS levels in liver tissue. Hyperthermic preconditioning at either 40 or 42°C applied 4 h prior to peritonitis induction returned all parameters to their normal levels, which is similar to the results of the sham laparotomy group. The results of TNF f values in preconditioned rats were varied according to the temperature that was applied. The levels were increased at 40°C, whereas they showed a decline at 42°C. Hyperthermic preconditioning prevented the oxidative damage in liver as well as TNF f elevation, particularly at 42°C. Results from this study suggest that hyperthermic preconditioning 4 h prior to the onset of septic events may improve the adverse outcome in sepsis.

Polyanionic polysaccharides reduce intra-abdominal adhesion and abscess formation in a rat peritonitis model.

Intra-abdominal infection is complicated by adhesion and abscess formation. We have assessed the adhesion- and abscess-reducing capacity of various solution volumes and concentrations of two polyanionic polysaccharides, hyaluronan (HA) and carboxymethylcellulose (CMC), in a rat peritonitis model. In 192 male Wistar rats a bacterial peritonitis was induced using cecal ligation and puncture. After 24 h the abdomen was reopened and the ligated cecum resected. Animals were randomized into three control groups, nine groups treated with various solution volumes (1 to 8 ml) containing different HA concentrations, and four groups treated with 1.7% CMC solution. Rats were killed at day 7, postoperatively, and adhesions were scored at five abdominal sites on a scale from 0 to 4. The presence and size of intra-abdominal abscesses were noted. Fifty-four rats (28%) prematurely died. There was no significant difference in mortality between treatment groups and controls. Treatment with CMC (P < 0.001) and low (0.2 and 0.4%) concentrations of HA (P < 0.005) significantly reduced intra-abdominal adhesion formation. High volumes of 0.2 and 0.4% HA were most effective (P = 0.01). The effect of CMC was volume independent. The incidence of abdominal abscesses was also significantly reduced by treatment with either CMC (P < 0.001) or low concentrations of HA (P < 0.001). With regard to abscess formation the effect was independent of the volume administered for HA, while low volumes of CMC were most effective (P < 0.005). Intraperitoneal treatment with either CMC or low-viscosity HA solution reduced intra-abdominal adhesion and abscess formation in a rat peritonitis model. The volume-induced reduction in adhesion formation suggests a hydroflotation effect of HA solution.

Reduced neutrophil sequestration in lung tissue after laparoscopic lavage in a rat peritonitis model.

Laparoscopy to treat abdominal infections is becoming more and more popular. The effects of the CO(2) pneumoperitoneum have not yet been completely clarified. In a rat peritonitis model, therefore, we investigated the influence of laparoscopic lavage in comparison with the conventional technique. A defined multibacterial fecal specimen was installed in the abdominal cavities of 80 rats. These animals were randomized to three groups: group 1 (n = 32), no intervention; group 2 (n = 24), conventional; group 3 (n = 24), laparoscopic lavage. At 1, 2, and 8 hours after the surgical intervention, animals were killed and autopsied. The main outcome measures were bacteremia, interleukin-6 (IL-6) in plasma and ascites, changes in the blood count, and myeloperoxidase (MPO) activity in lung, liver, kidney, and pancreas. Differences of bacteremia were not found. In the ascites a marked increase in IL-6 was observed after 8 hours, which was lower in the treatment groups than in the controls (p <0.025). MPO activity as a measure of the granulocytes present in the tissue showed significant changes only in lung tissue. Two hours after the surgical intervention, the MPO in the lung in the laparoscopy group was significantly lower than that in the controls and the laparotomy group. In conclusion, conventional and laparoscopic lavage reduce inflammation. In this model, laparoscopic lavage with a CO(2) pneumoperitoneum appeared to have no negative influence on the inflammatory reaction during the early postoperative phase. Reduced neutrophil sequestration in lung tissue following laparoscopic lavage reflects the lower level of trauma caused by laparoscopy.

Bacterial translocation in a non-lethal rat model of peritonitis.

Bacterial translocation from the gut may occur under a variety of different clinical circumstances and has been implicated in the development of multiple organ failure. The aim of this study was to determine the distribution of bacterial translocation occurring in a model of chemically induced peritonitis. We also sought to document the degree of the associated immune and inflammatory response. Though a midline laparotomy, rats were injected with 5 mg of zymosan (in 0.2 ml of saline) into the subomental space. After 4, 18, 24, 48 and 96 h, a number of endpoints evaluated: intraperitoneal cellular influx, TNF-alpha and interleukin-6 concentrations and myeloperoxidase activity. Bacterial cultures were initiated from the free peritoneal fluid, mesenteric lymph nodes, liver, lung, and kidney. Imprints were also made of the peritoneal mesothelial surface to determine its integrity. When comparing rats injected with zymosan with the controls, there was evidence of a peritoneal inflammatory response within 4 hours. Facultative gram negative bacteria were found to be growing in the mesenteric lymph nodes and in the peritoneal fluid at 48 h. Anaerobic organisms were also cultured from the peritoneal fluid at 48 h. No organisms were cultured from the liver, lung or kidneys. In addition there was a significant increase in intraperitoneal cell numbers (predominantly neutrophils, P < 0.05), myeloperoxidase activity (P < 0.05) and TNF-alpha and IL-6 concentrations (P < 0.05). There was extensive loss of the peritoneal mesothelial cells. The peritoneal inflammatory changes and bacterial translocation had resolved by 96 h. Bacterial translocation can be induced by the presence of an acute inflammatory focus in the peritoneal cavity. The translocation and inflammatory changes were associated with extensive loss of mesothelial cells. Nonetheless, these changes all resolved, indicating that the peritoneal cavity has a significant capacity to deal with such insults. A clearer understanding of the cellular and molecular events involved in the resolution phase could lead to improvements in the treatment of peritonitis.

Evaluation of the safety of recombinant P-selectin glycoprotein ligand-immunoglobulin G fusion protein in experimental models of localized and systemic infection.

P-selectin is a major component in the early interaction between platelets, endothelial cells, and inflammatory cells in the initial phases of the innate immune response. The major ligand for P-selectin is P-selectin glycoprotein ligand-1 (PSGL-1) and this ligand is expressed on the surface of monocyte, lymphocyte, and neutrophil membranes. A truncated form of recombinant human P-selectin glycoprotein ligand-1 has been covalently linked to immunoglobulin G (rPSGL-Ig) and this fusion peptide functions as a competitive inhibitor of PSGL-1. As an inhibitor of neutrophil-endothelial cell adherence, rPSGL-Ig is in early clinical development for the treatment of ischemia reperfusion injury. To determine the potential for deleterious effects from inhibition in P-selectin-mediated neutrophil attachment in the presence of bacterial infection, the effects of therapeutic doses of rPSGL-Ig were tested in three standard laboratory sepsis models. The experimental models included: the murine systemic Listeria monocytogenes infection model, the Pseudomonas aeruginosa bacteremia model in neutropenic rats, and the cecal ligation and puncture (CLP)-induced peritonitis model in rats. Recombinant human PSGL-Ig had no adverse effects on mortality or immune clearance in systemic bacterial infection in any of the three infection models. The PSGL-1 inhibitor did significantly decrease local neutrophil infiltration and bacterial clearance in the peritoneum following CLP, but this did not increase the systemic levels of proinflammatory cytokines, the quantitative levels of bacteremia, or the overall mortality rate following CLP. The results indicate that rPSGL-Ig did not exacerbate infection in these experimental sepsis models.

Functional Properties of Circulating and Transmigrated Neutrophils in a Rat Peritonitis Model

Using a rat peritonitis model, we examined the pattern of expression of adhesion molecules and H₂O₂ productivity of neutrophils by indirect immunofluorescence and flow cytometry. H₂O₂ production in blood neutrophils was significantly increased after peritonitis induction. The expression of CD11b and CD18 antigens on blood neutrophils was also significantly increased after peritonitis induction. In contrast, H₂O₂ production in peritoneal neutrophils was significantly lower than that in blood neutrophils. The expression of CD11b and CD45 antigens on peritoneal neutrophils was significantly higher than on blood neutrophils. Although no function has been assigned to LFA-1 on neutrophils, the expression of LFA-1 (CD11a/CD18) on peritoneal neutrophils was significantly decreased.

Effect of gentamicin-containing sponges on the healing of colonic anastomoses in a rat model of peritonitis.

To study the influence of gentamicin-containing sponges on the healing of colonic anastomoses in a rat model of peritonitis. Controlled laboratory study. University hospital, Belgium. 40 male Wistar rats. Peritonitis was caused by implantation of a gelatin capsule containing faeces and barium sulphate. The rats then had a colonic anastomosis. They were divided into 4 groups (n = 10 in each). The control group (no additional treatment); a second group in which a plain collagen sponge was wrapped around the anastomosis; a third group in which a gentamicin-containing collagen sponge was wrapped around the anastomosis; the last group in which the animals were given an intramuscular dose of gentamicin. Operative mortality, weight loss and anastomotic bursting pressure four days after the anastomosis. Seven rats died before necropsy but none in the last group. Peritonitis developed in all rats Weight loss was significantly higher in the plain collagen group. Bursting pressures were similar in the control and two gentamicin groups. In the plain collagen group all the anastomoses but one had broken down. There was no difference in bursting pressure between rats treated with gentamicin sponges or systemically, and controls. Healing was severely compromised when a plain collagen sponge was used.

The effects of inhibiting leukocyte migration with fucoidin in a rat peritonitis model.

To study the effects of fucoidin on leukocyte rolling and emigration and bacterial colonization in a peritonitis sepsis model in rats. A controlled study in 64 male Wistar rats, anesthetized and rendered septic by cecal ligation and puncture (CLP). Immediately after CLP 32 animals received a continuous infusion of fucoidin and 32 a continuous infusion of Ringer's lactate. Systemic leukocyte counts were determined every 2 h after CLP. Surviving animals were anesthetized 24 h after CLP, and intravital measurements of leukocyte rolling in venules in the cremaster muscle were performed. The animals were then killed and their organs harvested for histological and microbiological examinations. The 24-h survival was comparable in the two groups. Fucoidin-treated animals had higher leukocyte counts in the systemic circulation and lower counts in the lungs, liver, abdominal cavity, and brain than control animals. The number of bacterial colony forming units in the abdominal cavity, lungs, liver, brain and blood did not differ in the two groups. Fucoidin treatment changed the type of bacteria predominantly found in the examined organs from Escherichia coli to Pseudomonas aeruginosa. In an intra-abdominal model of sepsis we found that treatment with fucoidin induces leukocytosis inhibits leukocyte rolling and reduces leukocyte emigration in the abdominal cavity, lungs, and liver. Reduction in the number of emigrating leukocytes was not associated with an increase in bacterial counts found in the examined organs.

Immunomodulation with granulocyte–macrophage colony-stimulating factor and interleukin 2 in an experimental model of sepsis

Abstract Background Previous studies have demonstrated that immunomodulation with granulocyte–macrophage colony-stimulating factor (GM-CSF) reduces the mortality rate in an experimental model of sepsis, decreases levels of tumour necrosis factor in the serum and in the liver, and enhances neutrophil activity. It was also demonstrated recently that immunoprophylaxis with interleukin (IL) 2 can reduce the mortality rate in rats that have undergone caecal ligature and puncture (CLP). In fact, IL-2 is the major activator of the specific immune response (B and T lymphocytes). The aim of this study was to investigate whether IL-2 and GM-CSF together might further decrease the mortality rate in an experimental model of peritonitis in rats, which resembles the clinical situation of bowel perforation and mixed bacterial peritonitis. Methods Peritonitis was induced by CLP in four groups of Sprague–Dawley male rats (250 g). Each group included 30 rats. Group 1 underwent CLP and postoperative antibiotic therapy with tobramycin and clindamycin (12·5 μg g−1 day−1 and 4 mg g−1 day−1 respectively for 72 h after operation). Group 2 underwent preoperative intraperitoneal IL-2 injection (1.000.000 units), then CLP and postoperative antibiotic therapy with the same regimen. Group 3 underwent CLP and intraperitoneal GM-CSF injection (l ng g−1 day−1 for 48 h after operation). Group 4 received IL-2, CLP and GM-CSF with the same regimen and antibiotic therapy. Deaths were recorded within 72 h after CLP. Results After CLP group 1 (antibiotics) had a mortality rate of 70 per cent; group 4 (IL-2, GM-CSF, antibiotics) had a mortality rate of only 3 per cent which was significantly lower than in that in group 2 (IL-2 and antibiotics) and group 3 (GM-CSF and antibiotics), 33 and 25 per cent respectively (P &amp;lt; 0·0001). Conclusion Only one of 30 rats that had CLP and were treated with IL-2, GM-CSF and antibiotics died. Immunomodulation offers a new option in the treatment of sepsis related to peritonitis; in this experimental model treatment with IL-2 and GM-CSF enhanced host resistance to sepsis and decreased the mortality rate.

Prevention of intra-abdominal abscesses and adhesions using a hyaluronic acid solution in a rat peritonitis model: Reinjen MM, Meis JF, Postma VA, et al. Arch Surg 134:997, 1999

Prevention of intra-abdominal abscesses and adhesions using a hyaluronic acid solution in a rat peritonitis model: Reinjen MM, Meis JF, Postma VA, et al. Arch Surg 134:997, 1999