Ischemic Colonic Anastomoses Research Articles

The effect of carbon monoxide releasing molecule-2 (CORM-2) on healing of ischemic colon anastomosis in rats

Background/aimIschemia on the colon wall negatively affects healing of anastomosis. We were aimed to evaluate the effects of carbon monoxide releasing molecule-2 (CORM-2) on the healing of anastomosis in a rat model of the ischemic colon. Materials and methodsIn this prospective study a total of 60 rats were randomly divided into three groups as colon transection and end-to-end anastomosis (Group I), colon transection, and end-to-end anastomosis following the induction of ischemia (Group II), and colon transection and end-to-end anastomosis following the induction of ischemia and treated with daily intraperitoneal administration of CORM-2 (Group III). Each group was also divided into two equal subgroups as postoperative 3rd and 7th day. Postoperative healing of anastomoses was evaluated by anastomosis burst pressure (ABP), tissue biomarkers including hydroxyproline (HP), malondialdehyde (MDA), glutathione (GSH), and histopathological findings.ResultsIn the ischemic group treated with CORM-2, lower MDA and higher HP levels were observed in comparison to the untreated ischemic group on the 3rdday. GSH and HP levels were higher and MDA levels was lower in the ischemic rats treated with CORM-2 than in the ischemic untreated rats on the 7th day. In the ischemic group treated with CORM-2, the mucosal epithelial score decreased and the neoangiogenesis score increased compared to the untreated rats on the 7th day.ConclusionIn ischemic colon anastomosis, reduces cell destruction by suppressing the oxidative reaction, and strengthening the antioxidative mechanisms of the cells. It also increases collagen formation, epithelial development, and neoangiogenesis.

Effects of Duraseal® and Fibrin Glue on healing of normal and ischemic colon anastomosis

Background and Aims: Anastomotic leaks represent a major complication of colorectal surgery. This study, involving a rat model of normal and ischemic colon anastomosis, aims to compare the effects of Duraseal® with those of Fibrin Glue (FG). Methods: Fifty adult male Wistar Albino rats were divided into six groups; normal colon anastomosis, ischemic colon anastomosis, FG on normal colon anastomosis, Duraseal® on normal colon anastomosis, FG on ischemic colon anastomosis, Duraseal® on ischemic colon anastomosis. After scarification, bursting pressure were measured and samples were collected for histopathological examination and hydroxyproline assays. Results: While the mean bursting pressure was statistically higher in groups treated with Duraseal® when compared to controls (p<0.05), no significant differences between Duraseal® and FG were detected (p>0.05). The mean hydroxyproline level was significantly lower in the Duraseal® groups than in the FG groups (p<0.05). However, significant differences between Duraseal® and control groups were found only in ischemic colon anastomosis (p<0.05). Histopathological examinations did not show any differences in wound healing. Conclusion: Considering the advantages associated with the use of Duraseal®, we may assume that it may play role in gastrointestinal surgery with respect to prevention of anastomotic leaks. However, data is limited, and further studies are warranted to better define its place in surgery.

Effect of the wrapping of experimentally induced ischemic colonic anastomoses with the amniotic membrane on anastomosis safety in rats.

Objective: Colonic anastomotic leakage represents a complication with high mortality and morbidity. In the present study, it was aimed to examine the effect of the amniotic membrane on the healing of ischemic colonic anastomosis. Methods: 25 pregnant Wistar albino rats aged 19-21 days were randomly divided into 5 groups. With midline laparotomy, pregnancies were terminated, and fresh amniotic membranes were obtained. In Group 1 Sham (S), no procedure except for laparotomy was performed. In Group 2 of colonic anastomosis (A), the descending colon was completely transected and anastomosed. In Group 3 of amniotic anastomosis (AA), the anastomosis line was fixed by being wrapped with the fresh amniotic membrane. In Group 4 of colonic ischemic anastomosis (IA), the marginal arteries were ligated after descending colon transection. Ischemia was induced, and anastomosis was performed. In Group 5 of colonic ischemic anastomosis wrapped with the amniotic membrane (AIA), after ischemic colonic anastomosis was performed, the anastomosis line was fixed by being wrapped with the amniotic membrane. On the postoperative 7th day, rats were sacrificed, and their anastomotic bursting pressures were measured. For histological examination, the colon segment containing the anastomosis line was removed. Hematoxylin-eosin and Van Gieson trichrome stained specimens were histologically evaluated and scored according to the Ehrlich-Hunt model. Results: Anastomotic bursting pressures were measured in group S as the highest, in AA, AIA, A in a decreasing order and in group IA as the lowest. The difference between groups S and AA was statistically insignificant in the paired comparison of groups according to their bursting pressure values (p=0.222). When the other pairs were compared, the difference between the groups was calculated as significant (p< 0.05). According to the Ehrlich-Hunt model, the total score was the highest in AIA group, decreased in AA, IA, A groups in a decreasing order, and was the lowest in group S. A paired comparison for total scores between the groups was statistically insignificant between groups S and A (p=0.222). Other paired comparisons were statistically significant (p< 0.05). Conclusion: Wrapping the colon anastomosis line with the amniotic membrane gave positive results both in the ischemic colon as well as in the non-ischemic colon in terms of bursting pressure and histological anastomosis safety.

Healing of Ischemic Colon Anastomosis in Rats Could Be Provided by Administering Dexpanthenol or Coenzyme Q10.

Background: In this study, the effectiveness of dexpanthenol and coenzyme Q10 (CoQ10) on the healing of ischemic colon anastomosis was investigated. Methods: Forty eight male Wistar Albino rats were divided into four equal groups (Sham-S, Sham-I, DXP, Q10). Following full layer colon resection, single layer colon anastomosis, without creating ischemia, was performed on the Sham-S group. The same experimental model was performed on remaining groups after ischemia was created. Intraperitoneal dexpanthenol and CoQ10 was administered to the DXP and Q10 groups once a day for three days. Ten days later, all colon anastomoses were investigated histopathologically and biochemically, as well as their burst pressure values, in all sacrificed rats. Results: The highest burst pressure value was observed in the Sham-S group, decreasing from high to low in the DXP, Q10, and Sham-I groups, respectively (p = 0.008). Furthermore, tissue hydroxyproline (p = 0.001) level values were significantly different among the groups. Additionally, histopathological analysis revealed a significant difference among groups regarding reepithelization (p = 0.027) and polymorphonuclear leukocyte density (p = 0.022). Conclusions: This preliminary study has shown that ischemia-reperfusion injury may impair the healing of colon anastomosis and it has been concluded that dexpanthenol and CoQ10 may have positive effects on the healing of ischemic colon anastomosis in rat, although re-epithelization may be adversely affected using CoQ10.

Fluorescent test accurately predicts leak of ischemic colon anastomosis in rats.

To investigate if fluorescein fluorescent test can predict dehiscence in a model of ischemic colonic anastomosis in rats. This experimental controlled trial randomly assigned 55 rats to four groups. Anastomoses were performed in non-ischemic colon segments (control group) and in ischemic colon segments measuring 1, 2 or 3 cm long (groups 1, 2 and 3, respectively). Fluorescein was injected and the tissues were examined under ultraviolet light. Seven days later, a second-look surgery was performed to check for the presence or absence of anastomosis dehiscence. Twenty-four rats presented anastomotic dehiscence during the second-look surgery. Reticular and nonfluorescent patterns were significantly associated with the occurrence of anastomotic dehiscence. Fluorescein fluorescence had a sensitivity of 95.8%, specificity of 89.2%, positive predictive value of 88.4%, negative predictive value of 96.2%, and accuracy of 92.3% to predict anastomotic dehiscence. Fluorescein fluorescent test can accurately predict leak in a model of ischemic colonic anastomosis in rats.

Therapeutic improvement of colonic anastomotic healing under complicated conditions: A systematic review.

To identify therapeutic agents for the prophylaxis of gastrointestinal anastomotic leakage (AL) under complicated conditions. The PubMed and EMBASE databases were searched for English articles published between January 1975 and September 2014. Studies with the primary purpose of improving anastomotic healing in the colon or rectum under complicated preoperative and/or intraoperative conditions were included. We excluded studies investigating the adverse effects or risk assessment of an active intervention. Furthermore, investigations of biophysical materials, sealants, electrical stimulation and nutrients were excluded. The primary study outcome was biomechanical anastomotic strength or AL. The meta-analysis focused on therapeutic agents that were investigated in one animal model using the same outcome by at least three independent research groups. The 65 studies included were divided into 7 different complicated animal models: Bowel ischemia, ischemia/reperfusion, bowel obstruction, obstructive jaundice, peritonitis, chemotherapy and radiotherapy. In total, 48 different therapeutic compounds were examined. The majority of investigated agents (65%) were reported as beneficial for anastomotic healing. Twelve of the agents (25%) were tested more than once in the same model, whereas 13 (27%) of the agents were tested in two or more models of complicated healing. Two therapeutic agents met our inclusion criteria for the meta-analysis. Postoperative hyperbaric oxygen therapy significantly increased anastomotic bursting pressure in ischemic colon anastomoses by a mean of 28 mmHg (95%CI: 17 to 39 mmHg, P < 0.00001). Granulocyte macrophage-colony stimulating factor failed to show a significant increase in anastomotic bursting pressure (95%CI: -20 to 21 mmHg, P = 0.97) vs controls in experimental chemotherapeutic models. This systematic review identified potential therapeutic agents, but more studies are needed before concluding that any of these are useful for AL prophylaxis.

Fibrinogen and thrombin concentrations are critical for fibrin glue adherence in rat high-risk colon anastomoses

OBJECTIVE:Fibrin glues have not been consistently successful in preventing the dehiscence of high-risk colonic anastomoses. Fibrinogen and thrombin concentrations in glues determine their ability to function as sealants, healers, and/or adhesives. The objective of the current study was to compare the effects of different concentrations of fibrinogen and thrombin on bursting pressure, leaks, dehiscence, and morphology of high-risk ischemic colonic anastomoses using fibrin glue in rats.METHODS:Colonic anastomoses in adult female Sprague-Dawley rats (weight, 250-350 g) treated with fibrin glue containing different concentrations of fibrinogen and thrombin were evaluated at post-operative day 5. The interventions were low-risk (normal) or high-risk (ischemic) end-to-end colonic anastomoses using polypropylene sutures and topical application of fibrinogen at high (120 mg/mL) or low (40 mg/mL) concentrations and thrombin at high (1000 IU/mL) or low (500 IU/mL) concentrations.RESULTS:Ischemia alone, anastomosis alone, or both together reduced the bursting pressure. Glues containing a low fibrinogen concentration improved this parameter in all cases. High thrombin in combination with low fibrinogen also improved adherence exclusively in low-risk anastomoses. No differences were detected with respect to macroscopic parameters, histopathology, or hydroxyproline content at 5 days post-anastomosis.CONCLUSIONS:Fibrin glue with a low fibrinogen content normalizes the bursting pressure of high-risk ischemic left-colon anastomoses in rats at day 5 after surgery.

Is combined therapy more effective than growth hormone or hyperbaric oxygen alone in the healing of left ischemic and non-ischemic colonic anastomoses?

OBJECTIVE:Our aim was to investigate the effects of growth hormone (GH), hyperbaric oxygen and combined therapy on normal and ischemic colonic anastomoses in rats.METHODS:Eighty male Wistar rats were divided into eight groups (n = 10). In the first four groups, non-ischemic colonic anastomosis was performed, whereas in the remaining four groups, ischemic colonic anastomosis was performed. In groups 5, 6, 7, and 8, colonic ischemia was established by ligating 2 cm of the mesocolon on either side of the anastomosis. The control groups (1 and 5) received no treatment. Hyperbaric oxygen therapy was initiated immediately after surgery and continued for 4 days in groups 3 and 4. Groups 2 and 6 received recombinant human growth hormone, whereas groups 4 and 8 received GH and hyperbaric oxygen treatment. Relaparotomy was performed on postoperative day 4, and a perianastomotic colon segment 2 cm in length was excised for the detection of biochemical and mechanical parameters of anastomotic healing and histopathological evaluation.RESULTS:Combined treatment with hyperbaric oxygen and GH increased the mean bursting pressure values in all of the groups, and a statistically significant increase was noted in the ischemic groups compared to the controls (p<0.05). This improvement was more evident in the ischemic and normal groups treated with combined therapy. In addition, a histopathological evaluation of anastomotic neovascularization and collagen deposition showed significant differences among the groups.CONCLUSIONS:Combined treatment with recombinant human growth hormone and hyperbaric oxygen resulted in a favorable therapeutic effect on the healing of ischemic colonic anastomoses.

Adipose-tissue-derived Stem Cells Enhance the Healing of Ischemic Colonic Anastomoses: An Experimental Study in Rats

PurposeThis experimental study verified the effect of adipose-tissue-derived stem cells (ASCs) on the healing of ischemic colonic anastomoses in rats.MethodsASCs were isolated from the subcutaneous fat tissue of rats and identified as mesenchymal stem cells by identification of different potentials. An animal model of colonic ischemic anastomosis was induced by modifying Nagahata's method. Sixty male Sprague-Dawley rats (10-week-old, 370 ± 50 g) were divided into two groups (n = 30 each): a control group in which the anastomosis was sutured in a single layer with 6-0 polypropylene without any treatment and an ASCtreated group (ASC group) in which the anastomosis was sutured as in the control group, but then ASCs were locally transplanted into the bowel wall around the anastomosis. The rats were sacrificed on postoperative day 7. Healing of the anastomoses was assessed by measuring loss of body weight, wound infection, anastomotic leakage, mortality, adhesion formation, ileus, anastomotic stricture, anastomotic bursting pressure, histopathological features, and microvascular density.ResultsNo differences in wound infection, anastomotic leakage, or mortality between the two groups were observed. The ASC group had significantly more favorable anastomotic healing, including less body weight lost, less ileus, and fewer ulcers and strictures, than the control group. ASCs augmented bursting pressure and collagen deposition. The histopathological features were significantly more favorable in the ASC group, and microvascular density was significantly higher than it was in the control group.ConclusionLocally-transplanted ASCs enhanced healing of ischemic colonic anastomoses by increasing angiogenesis. ASCs could be a novel strategy for accelerating healing of colonic ischemic risk anastomoses.

Adrenomedulline improves ischemic left colonic anastomotic healing in an experimental rodent model

BACKGROUND:Leakage from colonic anastomosis is a major complication causing increased mortality and morbidity. Ischemia is a well-known cause of this event. This study was designed to investigate the effects of adrenomedullin on the healing of ischemic colon anastomosis in a rat model.METHODSStandardized left colon resection 3 cm above the peritoneal reflection and colonic anastomosis were performed in 40 Wistar rats that were divided into four groups. To mimic ischemia, the mesocolon was ligated 2 cm from either side of the anastomosis in all of the groups. The control groups (1 and 2) received no further treatment. The experimental groups (3 and 4) received adrenomedullin treatment. Adrenomedullin therapy was started in the perioperative period in group 3 and 4 rats (the therapeutic groups). Group 1 and group 3 rats were sacrificed on postoperative day 3. Group 2 and group 4 rats were sacrificed on postoperative day 7. After careful relaparotomy, bursting pressure, hydroxyproline, malondialdehyde, interleukin 6, nitric oxide, vascular endothelial growth factor, and tumor necrosis factor alpha levels were measured. Histopathological characteristics of the anastomosis were analyzed.RESULTSThe group 3 animals had a significantly higher bursting pressure than group 1 (p<0.05). Hydroxyproline levels in group 1 were significantly lower than in group 3 (p<0.05). The mean bursting pressure was significantly different between group 2 and group 4 (p<0.05). Hydroxyproline levels in groups 3 and 4 were significantly increased by adrenomedullin therapy relative to the control groups (p<0.05). When all groups were compared, malondialdehyde and nitric oxide were significantly lower in the control groups (p<0.05). When vascular endothelial growth factor levels were compared, no statistically significant difference between groups was observed. Interleukin 6 and tumor necrosis factor alpha were significantly decreased by adrenomedullin therapy (p<0.05). The healing parameters and inflammatory changes (e.g., granulocytic cell infiltration, necrosis, and exudate) were significantly different among all groups (p<0.05).CONCLUSIONAdrenomedullin had positive effects on histopathologic anastomotic healing in this experimental model of ischemic colon anastomosis.

Letter to the editor regarding the experimental study of Adas et al.: Mesenchymal stem cells improve the healing of ischemic colonic anastomoses

Dear Editor, We read with great interest the article by Adas G. et al., regarding an experimental study about mesenchymal stem cells and how they improve the healing of ischemic colonic anastomoses [1]. We would like to congratulate the authors for their great work which is very innovative. However, it would be very informative if the authors could provide details regarding the genetic lineage of the laboratory animals used, as well as the scoring criteria of the histopathological evaluation of necrosis, epithelialization, inflammatory processes, fibroblastic activity, neovascularization, and collagen deposition. Also, it would be very useful if the authors could provide additional information regarding the statistical analysis of the data. In particular, there is no description of how the sample size of each group of laboratory animals was defined. Was there any prior pilot study that described the variance? Furthermore, parametric statistical tests are used without any comment about the normality of the data. Finally, in Table 3, the statistical summarizing of the histopathological scoring assessment is not accurately interpreted. Median with interquartile range or with range is more appropriate than mean with standard deviation, as the data are ordinal. Maybe a different approach of the statistical evaluation of the data would not come to the same conclusions. Thank you for the communication opportunity. Reference

İskemik kolon anastomozlarının iyileşmesi üzerine pentoxifylline ve vinpocetinenin etkisi. (Deneysel Çalışma)

In the current study, we aimed to investigate the influences of pentoxifylline, which increases the flexibility, deformability and viscosity of the erythrocytes while reducing the aggregation abilities of the platelets, and vinpocetine, which has neuroprotective and antioxidant effects, on healing of colonic anastomoses. We used 30 Albino Wistar rats. Subjects were divided into three groups of 10 rats each. Colonic ischemia was established in all the groups. Following colonic transection, anastomosis was performed. Group A received intraperitoneal saline, whereas Group B and Group C received pentoxifylline and vinpocetine, respectively. The subjects were sacrificed on the postoperative 5th day by ether anesthesia, and their colonic bursting pressures were measured. The anastomotic area was excised for hydroxyproline assay and histopathologic examination. According to intergroup comparisons, colonic bursting pressure was found to be higher in the treatment groups than in the control group; however, the difference was not statistically significant. Intergroup comparisons regarding tissue hydroxyproline levels showed statistically significant differences between Groups A and B, Groups A and C and Groups B and C. Similar to pentoxifylline, vinpocetine was also shown to have a beneficial effect over ischemic colon anastomoses.

VEGF-A and FGF gene therapy accelerate healing of ischemic colonic anastomoses (experimental study)

Background Reducing ischemic damage is one of the goals of surgery. The aim of this study was to apply human VEGF-A and FGF-2 DNA-mediated gene therapy in order to identify their effects in the healing of ischemic colon anastomoses and eliminating the negative effects of ischemia. Methods Forty male Wistar albino rats weighing 250–280 g were divided into five equal groups ( n = 8) as follows: group 1: control, ischemic left colonic anastomosis; group; 2: ischemic left colonic anastomosis with control plasmid delivery; group 3: ischemic left colonic anastomosis with VEGF plasmid delivery; group 4: ischemic left colonic anastomosis with FGF plasmid delivery; group 5: ischemic left colonic anastomosis with VEGF and FGF plasmid delivery. All rats were sacrificed on the 4th postoperative day. Anastomosis burst pressures were measured for mechanical examination of anastomosis. Tissue hydroxyprolin, VEGF and FGF levels were determined as biochemical parameters. Necrosis, epithelisation, inflammatory processes, fibroblastic activity, collagen deposition and neovascularisation at the anastomic site were studied. Results VEGF, FGF and combined therapy significantly accelerated many of the histological parameters of healing, including fibroblast activation, collagen deposition, and angiogenesis, and augmented the levels of hydroxyproline and bursting pressure. Conclusions This is the first study to use gene therapy with growth factors for the healing of ischemic colonic anastomosis. This therapy can be effectively used in increasing ischemic anastomosis wound healing.

Mesenchymal stem cells improve the healing of ischemic colonic anastomoses (experimental study)

The goal of this study is to examine if allogenic mesenchymal stem cell (MSC) transplantation is a useful therapy for left ischemic colon anastomosis in rats. Problems with anastomosis healing may lead to serious postoperative complications. Bone marrow-derived mesenchymal stem cells (BM-MSCs), which are also referred to as stromal progenitor cells, are self-renewing and expandable stem cells. Recent studies have suggested that BM-MSCs play a crucial role in the processes of intestinal repair and accelerate angiogenesis. MSCs were isolated from rats before analysis by light and scanning electron microscopy. Forty male Wistar albino rats weighing 250-280 g were divided into four equal groups (n = 10) as follows: group 1: control, ischemic left colonic anastomoses (fourth day); group 2: control, ischemic left colonic anastomoses (seventh day); group 3: ischemic left colonic anastomoses + locally transplanted BM-MSCs (fourth day); group 4: ischemic left colonic anastomoses + locally transplanted BM-MSCs (seventh day). Histopathological features and anastomotic strength were evaluated. BM-MSCs therapy significantly accelerated all of the healing parameters for ischemic colonic anastomosis except for inflammation on the fourth day. On the seventh day, BM-MSCs augmented the levels of the hydroxyproline and bursting pressure. Histological parameters, especially angiogenesis, were also found to be important for healing of ischemic colonic anastomoses. This is the first study to use locally transplanted cell therapy for the healing of ischemic colonic anastomosis. BM-MSCs therapy significantly accelerated all of the healing parameters for ischemic colonic anastomosis.

Effect of 2-Octyl-Cyanoacrylate on Ischemic Anastomosis of the Left Colon

Introduction: 2-octyl-cyanoacrylate may be a good alternative in ischemic colon anastomosis without impairment of tissue perfusion. Methods: Forty male Wistar albino rats were randomized into four experimental groups (n = 10 in each group). In group 1 (control), a well-perfused left colonic segment was transected, and free ends were anastomosed by propylene sutures. In groups 2, 3, and 4, the animals underwent a standardized surgical procedure to induce ischemic left colon anastomosis. In group 2, an end-to-end anastomosis was created using six interrupted 6-0 polypropylene sutures between ischemic edges. In group 3, after approximating the mesenteric and antimesenteric edges of the anastomosis with two 6-0 polypropylene sutures, 2-octyl-cyanoacrylate was applied between the edges. In group 4, anastomosis was created by the same technique as described in group 2, and additionally 2-octyl-cyanoacrylate was applied on suture line. Rats were killed on day 4 following operation. Anastomotic integrity, intraperitoneal adhesion scores, anastomotic bursting pressures, and tissue hydroxyproline levels were recorded. Histopathological examination of the anastomosis was also performed. Results: There were no statistically significant differences among groups with respect to anastomotic integrity (p =.142). The mean bursting pressure values were 81.1 ± 23.83, 43.3 ± 26.06, 15.8 ± 11.3, and 17.6 ± 18.02 in groups 1, 2, 3, and 4, respectively. There were no statistically significant differences among groups 2, 3, and 4 with respect to tissue hydroxyproline levels and bursting pressure levels. The highest adhesion scores were observed in groups 3 and 4. Discussion: 2-octyl cyanoacrylate does not have additional advantages in the healing of experimental ischemic colon anastomosis.

Does sildenafil reverse the adverse effects of ischemia on ischemic colon anastomosis: Yes, ‘no’

Introduction Sildenafil may lead an improvement in anastomotic healing of ischemic left colon anastomosis. Methods Thirty-six male Wistar albino rats were randomized into four experimental groups ( n = 9 in each group). In group 1, a well-perfused left colonic segment was transected, and free ends were anatomosed. In groups 2, 3 and 4 animals underwent a standardized surgical procedure to induce ischemic left colon anastomosis. Group 2 animals received only tap water. In groups 3 and 4 animals received 10 mg/kg/body-weight and 20 mg/kg/body-weight sildenafil, single dose a day during 4 days, respectively. Rats were sacrificed on day 4 following operation. Anastomotic integrity, intra-peritoneal adhesion scores, anastomotic bursting pressures and tissue hydroxyproline levels were recorded. Histopathological examination of the anastomosis was also performed. Results There was no statistically significant difference among groups with respect to anastomotic integrity ( p = 0.142) but ischemia decreased the anastomotic bursting pressure. The mean bursting pressure values were 78.8 ± 24.1, 43.3 ± 26, 55.1 ± 32.4, and 43.3 ± 20.4 in groups 1, 2, 3, and 4, respectively. Group 1 had the highest values whereas; there was no statistically significant difference between groups 1 and 3. There was no statistically significant difference among groups 2, 3, and 4 with respect to tissue hydroxyproline levels, adhesion scores and the Chiu scores. The highest inflammatory cell presence in the granulation tissue was detected in group 2, whereas the lowest was detected in group 4 ( p = 0.0001). The highest fibroblast infiltration in the granulation tissue was detected in group 1 ( p = 0.045). Discussion Our results showed that 10 mg/kg sildenafil decreased the adverse effects of ischemia on the healing of ischemic left colon anastomosis. Additional investigations are needed to confirm the effects of phosphodiesterase-5 inhibitors in ischemic colon anastomosis models.

The Effects of Sildenafil Citrate on Ischemic Colonic Anastomotic Healing in Rats: Its Relationship Between Nitric Oxide and Oxidative Stress

The purpose of this study was to examine the effects of sildenafil citrate on normal and ischemic colon anastomosis in the rat model by measuring the levels of blood and colonic tissues nitric oxide, thiobarbituric acid reactive substrates (as a marker of lipid peroxidation), and glutathione (as an antioxidant). Normal (group 1 and 3) and ischemic anastomosis (group 2 and 4) were performed in four equal rat groups (n = 14). Orally 10 mg/kg per day of sildenafil citrate therapy were applied in group 3 and group 4 after operation. Seven rats of the each group were killed on postoperative days 3 and 7. Sildenafil citrate therapy was resulted in elevated nitric oxide levels in both normal and ischemic anastomotic tissues (p < 0.0001 and p < 0.03) at postoperative day 3. Tissue thiobarbituric acid reactive substrate levels were elevated in rats with normal anastomosis by sildenafil therapy (p < 0.001) at postoperative days 3 and 7 (p < 0.05). Sildenafil therapy given to the normal anastomosis group has significantly higher tissue nitric oxide levels than the normal anastomosis group without therapy at postoperative day 7 (p < 0.001). On postoperative day 7, plasma nitric oxide levels were decreased by sildenafil citrate in rats with normal (p < 0.01) and ischemic anastomosis (p < 0.05). The beneficial effect of sildenafil citrate also was seen for erythrocyte glutathione levels in rats with normal anastomosis at postoperative day 7 and in rats with ischemic anastomosis at postoperative day 3. Our results suggest that sildenafil citrate may affect ischemic anastomotic healing due to its possible effects on nitric oxide metabolism and lipid peroxidation. However, functional implication of this agent further needs to be elucidated.

Preoperative and Postoperative Administration of Hyperbaric Oxygen Improves Biochemical and Mechanical Parameters on Ischemic and Normal Colonic Anastomoses

Colonic anastomotic leaks are a major postoperative complication, causing increased mortality and morbidity. Tissue ischemia is one of the most important factors that disrupt anastomotic healing. It is possible to reverse inadequate tissue oxygenation by using increased atmospheric pressure and hyperoxia, which are obtained from hyperbaric oxygen treatment (HBO). Our aim was to investigate the effects of preoperative and postoperative HBO treatment on normal and ischemic colonic anastomoses in rats. Eighty male Wistar Albino rats, weighing between 180 and 240 g, were divided into 8 equal groups. A 1-cm segment of left colon was resected 3 cm proximal to the peritoneal reflection in all groups and colonic anastomosis was performed. In groups 2, 4, 6 and 8, colonic ischemia was established by ligating 2 cm of mesocolon on either side of the anastomosis. Control groups (1 and 2) received no HBO. HBO treatment was given preoperatively in groups 3 and 4, postoperatively in groups 5 and 6, and both preoperatively and postoperatively in groups 7 and 8. HBO treatment was applied for 2 days in the preoperative period and 4 days in the postoperative period. Relaparotomy was performed on postoperative day 5 and a perianastomotic colon segment 2 cm in length was excised for detection of biochemical and mechanical parameters of anastomotic healing and histopathological evaluation. HBO treatment increased tissue hydroxyproline levels in all groups, and this difference was significant in normal anastomosis groups receiving preoperative HBO compared to controls (p =. 013 for group 1 vs. group 3; p =. 023 for group 1 vs. group 5). This improvement was more evident in ischemic and normal groups treated by administration of combined pre- and postoperative HBO (p =. 021 and p =. 013). HBO treatment also increased the mean bursting pressure values in all groups, and again, a statistically significant increase was noted in the ischemic groups compared to controls (p =. 002 for group 2 vs. group 6; p =. 001 for group 2 vs. group 8). Histopathological evaluation of anastomotic line fibrosis was not found to show significant differences between the groups. Adequate tissue oxygenation is the main factor in wound and anastomosis healing. HBO treatment has a positive effect on biochemical and mechanical parameters of ischemic and normal colon anastomoses in rats. It is possible to see this effect more clearly with combined HBO treatment applied before and after ischemic anastomosis.

Effects of hyperbaric oxygen and Pgg-glucan on ischemic colon anastomosis

In colorectal surgery, anastomotic failure is still a problem in ischemia. Here,we analyzed the effects of hyperbaric oxygen and beta-glucan on colon anastomoses in ischemic condition. Colonic resection and anastomosis in rectosigmoid region were done in forty Wistar-Albino rats of four groups of equal number. Colon mesentery was ligated to induce ischemia. The first group was the control group. The subjects of second group were treated with hyperbaric oxygen;the third group with glucan and the forth group were treated with both. At the forth day, rats were sacrificed,anastomotic segment was resected and burst pressures and hydroxyproline levels of anastomotic line were measured. The burst pressure difference of second and third groups from the control group were meaningful (P<0.01); the forth group differed significantly from the control (P<0.001). There was no difference between the treated groups on burst pressure level (P>0.05). The hydroxyproline levels in all treated groups were different from the control group significantly (P<0.001). Hydroxyproline levels in the forth group were higher than those of the second and the third groups (P<0.001). There were no significant differences between the second and the fourth groups in burst pressure and hydroxyproline levels (P>0.05). Hyperbaric oxygen and glucan improve healing in ischemic colon anastomoses by anti-microbic,immune stimulating properties and seem to act synergistically when combined together.

The effect of Bosentan on healing of colonic anastomosis

BackgroundIschemia is the most important factor compromises wound healing in colonic anastomosis. Mesenteric vessels are ligated at first while performing colonic resection and following anastomosis. Therefore blood supply of the related segments of colon temporarily interrupted and ischemia can easily occur. This study was carried out to explore whether Bosentan, an endothelin-receptor antagonist, can eliminate vasoconstruction, increase blood flow in the splanchnic area and anastomotic region and therefore possibly facilitate wound healing and prevent intra-abdominal adhesion formation.MetodsStudy is conducted on 30 female Wistar-Albino rats weighing 180–240 gr. Rats were allocated into three groups. Group 1 (n = 10) recevied full-thickness resection of the left colon and end-to-end anastomosis. In Groups 2 (n = 10) and 3 (n = 10), vessels of 2–3 cm segment of the left colon were ligated, indications of necrosis of that segment were expected, followed by resection and end-to-end anastomosis. Two milliliter of saline and 5 mg/kg Bosentan was given intraperitoneally in Group 2 and 3, respectively. On postoperativ day 6, intra-abdominal adhesions were scored. Healing of anastomosis, anastomotic bursting pressures, tissue hydroxyproline levels and histopatologically healing scores were assessed.ResultsMacroscopic adhesion score in Group 3 was lower than the remained groups (p < 0.05). Tissue hydroxyproline levels were significantly higher in Group 3 compared to the Groups 1 and 2 (p < 0.001). Mean anastomotic bursting pressures were 200 mmHg, 164 mmHg and 240 mmHg in Groups 1, 2 an 3, respectively (p < 0.05 between Groups 1 and 3; p < 0.001 between Groups 2 and 3). Histopathologically, healing scores of Group 1 were significantly higher than the other groups (p < 0.05 group 1–3, group 2–3).ConclusionBosentan increases anastomotic healing of ischemic colonic anastomosis and decreases intra-abdominal adhesion formation.