Anastomotic Healing In Rats Research Articles

The effect of Ginkgo biloba EGb 761 on intestinal anastomotic healing in rats with ischemia-reperfusion induced in the lower extremities

Background/Aim: Remote ischemia-reperfusion (I-R) injury for anastomotic healing is a newly identified risk factor and there is a wide array of studies being conducted. This study aimed to reveal the negative effects of lower I-R on the colonic anastomotic healing process and examine the effects of Ginkgo biloba EGb 761 treatment, a platelet activating factor (PAF) antagonist, on anastomotic healing through the inhibition of pathological mechanisms of mediators causing these negative effects. Methods: Thirty-six Wistar-Albino rats were divided into sham, I-R and I-R+EGb 761 groups, each consisting of 12 rats. In the subjects in the sham group, an end-to-end anastomosis was performed by transecting the descending colon following midline laparotomy. In the I-R group, unilateral lower extremity ischemia was created by occluding the femoral artery and collaterals using a tourniquet from the most proximal segment of the left extremity. Then, the descending colon was transected, anastomosis was performed, and reperfusion was created by a tourniquet application at the 30th minute of ischemia. Different from the I-R (control) group, the subjects in the I-R+EGb 761 group were given two equal doses of 64 mg/kg/d Ginkgo biloba EGb 761 by the orogastric route until 10 days after surgery. After all subjects were sacrificed on the 10th day of surgery, the descending colon segment containing the anastomosis area was resected and samples were taken for bursting pressure and hydroxyproline measurements. Results: In the I-R group, anastomotic bursting pressure and perianastomotic hydroxyproline values were significantly lower compared to the sham group and the I-R+EGb 761 group. However, there was no statistically significant difference in these parameters between the sham and the I-R+EGb 761 groups. Conclusion: Colonic anastomotic bursting pressure and peri-anastomotic hydroxyproline values in the sham group were significantly decreased by lower extremity I-R, and this change was prevented with the use of EGb 761.

Early enteral nutrition with L-glutamine improves anastomotic healing in rats administered hyperthermic intraperitoneal chemotherapy with cisplatin and 5-FU

Background/Aim: One of the most significant aspects of intestinal surgery is anastomotic wound healing. After intestinal surgery, the most serious complication is gastrointestinal leakage, which is associated with a high rate of morbidity and mortality. The rate of morbidity and mortality can be reduced by increasing the mechanical resistance of the anastomosis. Glutamine improves impaired wound healing through effects on the healing process. This study investigated the effects of early enteral glutamine supplementation on colonic anastomosis healing in rats treated with hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin and fluorouracil (5-FU). Methods: Twenty-four rats were divided into three groups. Group 1 underwent colonic anastomosis and intraabdominal hyperthermic saline administration, Group 2 underwent colonic anastomosis and HIPEC, and Group 3 underwent colonic anastomosis and HIPEC and postoperative administration of glutamine solution via an orogastric tube for 7 days. On day 7, all rats were sacrificed and anastomotic bursting pressure (ABP) was evaluated. Tissue specimens were taken to examine tissue hydroxyproline levels and histopathological changes in the anastomotic line. Results: The ABP was significantly greater in Group 2 than in Groups 1 and 3 (P=0.001 and P=0.046, respectively). The tissue hydroxyproline level was higher in Group 1 and Group 3 than in Group 2 (P=0.001 and P=0.043, respectively). The histopathological findings in Group 3 were better than those in Group 2. The histopathological findings were observed to improve in the early enteral nutrition with Glutamine group. Conclusions: The findings of this study indicate that early enteral glutamine supplementation facilitates colonic anastomosis healing following HIPEC with cisplatin and 5-FU, by increasing the ABP and tissue concentrations of hydroxyproline and decreasing the inflammatory response.

The effects of iloprost on colonic anastomotic healing in rats under obstructive ileus conditions

BackgroundThe aim of this study was to investigate the effects of iloprost, on colonic anastomotic healing in rats, under obstructive ileus conditions. Materials and methodsEighty male Albino rats were randomized into four groups of 20 animals each. They underwent colonic resection followed by an inverted anastomosis. The rats of group 1 (control) and group 2 (ileus) received 3 mL of saline 0.9% intraperitoneally and those of group 3 (iloprost), and group 4 (ileus + iloprost) iloprost (2 μg/kg of body weight), immediately postoperatively and daily until the day of sacrifice. Each group was further divided into two equal subgroups, depending on the day of sacrifice. The animals of subgroup “a” were sacrificed on the fourth postoperative day, whereas those of “b” on the eighth day. Macroscopic and histologic assessment was performed, whereas anastomotic bursting pressures and the tissue concentrations in hydroxyproline and collagenase I were evaluated. ResultsMeans of bursting pressure, neoangiogenesis, fibroblast activity, and hydroxyproline concentration were significantly increased in group 4 compared with group 2. In addition, on the fourth postoperative day, the inflammatory cell infiltration and the collagenase I concentration were significantly decreased in group 4 compared with group 2. Moreover, on the eighth postoperative day, collagen deposition was significantly increased in group 4 compared with group 2. ConclusionsIloprost after intraperitoneal administration reverses the negative effect of obstructive ileus. It promotes not only the angiogenic activity but also collagen formation, resulting in increased bursting pressures on the fourth and eighth postoperative days.

Effects of β-Glucan on Colon Anastomotic Healing in Rats Given Preoperative Irradiation

ABSTRACTBackground: Radiation therapy is an essential therapeutic modality in the management of a wide variety of tumors. We aimed to investigate the short-term effects of pelvic irradiation on the healing of colon anastomoses and to determine the potential protective effects of β-glucan in this situation. Material and Methods: Sixty Wistar albino rats were randomized into three experimental groups: a control group (n = 20), an irradiation (IR) group (n = 20), and an irradiation+β-glucan (IR+β-glucan) group (n = 20). Only segmental colonic resection and anastomosis were performed on the control group. The IR group underwent the same surgical procedure as the control group 5 days after pelvic irradiation. In the IR+β-glucan group, the same procedure was applied as in the IR group after β-glucan administration. The groups were subdivided into subgroups according to the date of euthanasia (third [n = 10] or seventh [n = 10] postoperative [PO] day), and anastomotic colonic segments were resected to evaluate bursting pressures and biochemical and histopathological parameters. Results: Bursting pressure values were significantly lower in the IR group (p < .001). Malondialdehyde (MDA) levels were significantly higher in the IR group, whereas β-glucan significantly decreased MDA levels on the third PO day (p < .001). Granulation tissue formation scores were significantly lower in the IR+β-glucan group compared with the control group and the IR group (p < .001). Conclusions: The results of this study indicate that irradiation has negative effects on the early healing of colon anastomoses. The administration of β-glucan ameliorates these unfavorable effects by altering bursting pressures and biochemical parameters.

The effects of Pycnogenol® on colon anastomotic healing in rats given preoperative irradiation

Pycnogenol® has excellent radical scavenging properties and enhances the production of antioxidative enzymes which contributes to the anti-inflammatory effect of the extract. Irradiation delivered to the abdominal region, typically results in severe damage to the intestinal mucosa. The effects of ionizing radiation are mediated by the formation of free radicals through radiolysis. Irradiation has local effects on tissues. These local effects of irradiation on the bowel are believed to involve a two-stage process which includes both short and long term components. In our study we aimed to investigate the short term effects of Pycnogenol® on the healing of colon anastomoses in irradiated bowel. Sixty male Wistar-Albino rats were used in this study. There were three groups: Group I, control group (n = 20); group II which received preoperative irradiation (n = 20); group III which received per oral Pycnogenol® before irradiation (n = 20). Only segmeter colonic resection and anastomosis was performed to the control group (Group I). The other groups (Group II, III) underwent surgery on the 5th day after pelvic irradiation. On postoperative days 3 and 7, half of the rats in each group were sacrificed and then relaparotomy was performed. There was no statistical difference between groups with respect to biochemical parameters. Bursting pressure was significantly higher in the Control and Group III compared with the Group II. In conclusion, the present study showed that preoperative irradiation effect negatively on colonic anastomoses in rats by means of mechanical parameters and administration of Pycnogenol® preoperatively ameliorates this unfavorable effect.

Searching for the molecular benchmark of intestinal anastomotic healing in rats: an experimental study

Objective: Intestinal anastomotic healing processes differ greatly from analogous more widely-researched cutaneous phenomena. To date, we still lack comprehension of the particularities of the physiology of intestinal healing. Here, we examine the mRNA response time course to formation of an anastomosis.

Liver cirrhosis on the colonic anastomotic healing in rats

To investigate the effects of cirrhosis on colonic anastomosis healing in rats. Fifty five Wistar male rats were used (23 in the control group and 32 in the cirrhosis group). On the first day of the procedure, the rats in the cirrhosis group underwent double ligation and folding of the common bile duct to induce liver cirrhosis, and the control rats underwent a laparotomy and intestinal manipulation. On the fourteenth and thirty-fifth days, all of the animals were biochemically assessed for serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, bilirubin, total protein, and albumin and for liver histopathology. On the thirty-fifth day, cirrhosis was confirmed. On the twenty-eighth day, all of the animals were subjected to left colon transection and anastomosis. On the seventh day after the colonic anastomosis, the rats were sacrificed and macroscopically evaluated for dehiscence. The region of the colonic anastomosis was removed and subjected to hydroxyproline content measurement, conventional histology, and the immunohistochemical determination of vascular endothelial growth factor (VEGF) and matrix metalloproteinase type 1 (MMP 1). The biochemical and histopathological examinations confirmed cirrhosis in all of the animals in the cirrhosis group. More deaths occurred after anastomosis in the cirrhosis group (5/25) than in the control group (0/21), and anastomotic dehiscence was more frequent in the cirrhosis group (8/25) than in the control group (0/21). The average hydroxyproline concentration was lower in the cirrhosis group than in the control group. The immunohistochemical studies showed that the average VEGF expression in the cirrhosis group was lower than in the control group, and the average MMP1 expression was higher in the cirrhosis group. Hepatic cirrhosis leads to increased mortality and colonic anastomotic dehiscence, an increased distance between the mucosal edges of the anastomosis area, and a lower hydroxyproline concentration in the colonic anastomosis; therefore, these conditions are deleterious to healing.

The effects of tacrolimus on colonic anastomotic healing in rats

The aim of this experimental study is to investigate the effects of tacrolimus on colonic anastomotic healing after subcutaneous administration. Forty Albino-Wistar male rats were divided into two groups, with two equal subgroups each. They all underwent colonic resection followed by a single-layer, inverted colon anastomosis and were injected subcutaneously with either 1 ml of 0.9% NaCl solution or tacrolimus (0.1 mg/kg body weight) depending on their group. Half of the rats were sacrificed on the fourth postoperative day, while the remaining half were sacrificed on the eighth postoperative day. Macroscopical and histological assessment was performed, while anastomotic bursting pressures and the tissue concentrations in hydroxyproline and collagenase I were evaluated. On the fourth postoperative day, the bursting pressures (217.00 ± 11.12, p < 0.001), the fibroblast activity (2.80 ± 0.42, p = 0.022), the neoangiogenesis (2.10 ± 0.32, p = 0.007) and the tissue hydroxyproline concentration (254.23 ± 67.10, p = 0.001) were significantly higher in the tacrolimus-treated animals. Furthermore, tacrolimus significantly decreased the inflammatory cell infiltration (1.50 ± 0.53, p < 0.001) and the tissue collagenase I concentration (4.16 ± 0.76, p = 0.002). On the eighth day, the bursting pressure (264.00 ± 32.61, p < 0.001) and the hydroxyproline tissue concentration (331.04 ± 55.56, p = 0.002) were significantly higher in the tacrolimus subgroups. The inflammatory cell infiltration (1.20 ± 0.42, p < 0.001) and the collagenase I concentration (1.61 ± 0.83, p < 0.001) were significantly lower. In addition, the adhesion formation score was significantly lower (1.20 ± 0.92, p = 0.065). Tacrolimus, when injected subcutaneously, promotes healing of colonic anastomoses in rats. It impairs not only inflammatory response but also collagen degradation, resulting to increased anastomotic strength on the fourth as well as on the eighth postoperative day.

The effects of iloprost on colonic anastomotic healing in rats

The purpose of this experimental study is to investigate the effects of iloprost on colonic anastomotic healing in rats, after intraperitoneal administration. Forty male Albino-Wistar rats were randomized into two groups of twenty animals each. They all underwent colonic resection followed by an inverted anastomosis. The rats of Group A (control) received 3 ml of NaCl intraperitoneally, while those of Group B (iloprost) received iloprost (2 μg/kg body weight), immediately postoperatively and daily until killed. Each group was further divided into two equal subgroups, depending on the day of killing. The animals of subgroups 1 were killed on the fourth postoperative day, while those of subgroups 2 on the eighth. Macroscopical and histological assessments were performed. Besides, anastomotic bursting pressures and the tissue concentrations in hydroxyproline and collagenase I were also evaluated. No anastomotic dehiscence was noted. The mean bursting pressure was higher in the iloprost group compared with the control group, but a significant difference was revealed only on the fourth postoperative day. Furthermore, iloprost significantly increased the new vessel formation on the fourth, as well as on the eighth postoperative day. Iloprost enhances the early phase of colonic anastomotic healing in rats.

Effects of Platelet-Rich Plasma on Intestinal Anastomotic Healing in Rats: PRP Concentration is a Key Factor

Few studies have examined the effects of platelet-rich plasma (PRP) on intestinal anastomotic healing. The applied preparation methods and PRP concentrations used in the few studies that have been carried out varied markedly. Therefore, the positive effects of PRP on the anastomotic healing process remain unclear. The aim of this study is to examine the effects of different concentrations of PRP on intestinal anastomotic healing. From SD rat blood, three different concentrations of plasma were prepared: high-concentrated PRP (H-PRP: platelet count 5 × 10(6)/mm(3)), low-concentrated PRP (L-PRP: 2 × 10(6)/mm(3)), and platelet-poor plasma (PPP). Male SD rats underwent proximal jejunal anastomosis and central venous catheterization. Rats were divided into four groups (n = 12 for each group): control, PPP, L-PRP, and H-PRP groups. Two types of PRP and PPP (0.21 mL) were applied to each anastomosis line, with the exception of the control group. Total parenteral nutrition (TPN) solutions were administered (151 kcal/kg/d). Five days after surgery, anastomotic bursting pressure (ABP) in situ and hydroxyproline concentration (HYP) in anastomotic tissue were evaluated. The ABP values of control, PPP, L-PRP, and H-PRP groups were 171 ± 20, 174 ± 23, 189 ± 17, and 148 ± 25 mmHg, respectively. The HYP values of each group were 516 ± 130, 495 ± 123, 629 ± 120, and 407 ± 143 μg/g dry tissue. Compared with the other groups, the L-PRP group exhibited a significant increase in both ABP and HYP, while the H-PRP group exhibited a significant decrease in these two variables. As a result, L-PRP was considered to promote anastomotic wound healing, but H-PRP was considered to inhibit it. There was no significant difference between the PPP group and the control group. PRP concentration plays a crucial role in the efficacy of PRP. PRP might exert positive effects on intestinal anastomotic healing in a dose-dependent manner up to a certain level, but adverse effects occur when it is highly concentrated. The essential PRP action appears to be driven by the platelets themselves.

Pitfalls and Technical Aspects during the Research of Intestinal Anastomotic Healing in Rats

Background: Fundamental experimental research into intestinal anastomotic healing in rodent models will gain increasing interest in the future. Methods: The aim of this study was to describe our 5-year experience with a standardized experimental setup of small and large bowel anastomoses in a rodent model and present a basic set of assessment tools investigating anastomotic healing. Anastomotic technique, perioperative complications such as anastomotic insufficiency (AI) and obstructive ileus were in the focus. Results: During different studies with varying study patterns, 167 rat small bowel anastomoses and 120 colonic anastomoses were performed. Overall mortality was 3.6% in small bowel and 2.5% in colonic anastomoses, AI occurred in 2.9 and 4%, respectively. A postoperative obstructive ileus was seen in 3/167 small bowel anastomoses and none in the colonic group. Conclusion: When performing experimental intestinal anastomoses in a standardized operative setting and critically considering special perioperative issues, the incidence of relevant complications can be maintained at an adequately low level.

The effect of bevacizumab on colon anastomotic healing in rats

The aim of the study was to investigate the effect of angiogenesis inhibition by bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF) antibody, on the healing process of colonic anastomoses in rats, assessing some specific involved factors. This new agent is used mainly in metastatic colorectal cancer. The angiogenesis plays an important role in both wound healing and metastatic invasion and spread of malignant cells. There has not been any evidence assessing the optimal time for its safe use in operated patients. Forty Wistar rats were randomly allocated into four equal groups. A colonic anastomosis was performed in all rats. Half of them received intraoperatively a single dose of bevacizumab 5 mg/body weight and the rest received placebo. The animals were sacrificed on the 7th (Avastin 7th, placebo 7th) and 14th (Avastin 14th, placebo 14th) postoperative day. The anastomosis was resected and sent for histological study and for tissue biochemical assays (VEGF, endothelin-1 (ET-1), C-reactive protein (CRP), pro-oxidant-antioxidant balance (PAB), carbonylated proteins, hydroxyproline) using specific enzyme-linked immunosorbent assay kits. For statistical analysis, the Mann-Whitney U test was used (of statistical significance when P < 0.05). No complication or anastomotic dehiscence was observed. Histology did not reveal statistically significant differences between groups concerning degree of inflammation, fibroblasts, collagen, and fibrosis. Likewise, hydroxyproline levels did not differ. However, some statistically significant differences were found in VEGF, CRP and carbonyl proteins (Avastin 7th vs placebo 7th, placebo 14th vs placebo 7th), ET-1, and PAB (Avastin 14th vs Avastin 7th), which did not finally affect the collagen synthesis marker hydroxyproline, nor did the anastomotic strength. Bevacizumab, when administered intraoperatively, has no significant effect on colon anastomotic healing in rats despite a transient mild ischemia.

Rupture point analysis of intestinal anastomotic healing in rats under the action of pure Copaíba (Copaifera Iangsdorfii) oil

Analyze the mechanical strength of digestive tract scar after intestinal anastomosis surgery in animals treated with pure Copaíba oil. 60 Wistar rats, male, about 250 days old and weighting around 350g were used. The rats were randomly divided into two groups: Group O, with 30 animals that received Copaíba oil and Group C, with 30 animals that received saline. Each group was subdivided into three subgroups, containing 10 rats each. They were designated O7, O14, O28, C7, C14 and C28, according to the post-operative assessment date at 7, 14 and 28 days, respectively. On these dates euthanasia was performed with the removal of the bowel segment containing the anastomosis and assigning the samples to tensile test for assessing Maximum Stress, Maximum Tensile Strength and Maximum Rupture Strength. On the three variables of the study, the results indicate that, for the three assessment periods (7, 14 and 28 days) there was no significant difference between the oil and control groups. For the mechanical tests proposed by this study, Copaíba oil didn t show any effectiveness in increasing the anatomosis strength.

Effects of Nuclear Factor-κB Inhibitors on Colon Anastomotic Healing in Rats

Nuclear factor (NF)-κB plays an essential role in inflammation. We tested this role by administering NF-κB-inhibitors into rats undergoing a well-established model of colonic anastomotic healing. Wistar rats underwent laparotomy, descending colonic transection, and handsewn reanastomosis. The animals were randomized to receive either a selective NF-κB inhibitor (parthenolide 0.5 mg/kg or resveratrol 0.5 mg/kg) or an equal volume of water by gavages before operation and then daily after surgery. Animals were sacrificed either immediately after anastomotic construction (d 0) or at the third, fifth, or seventh postoperative day. Both parthenolide and resveratrol treatment led to early significant increases in plasma levels of IL-6. On d 7, hydroxyproline levels were significantly higher in the parthenolide and resveratrol groups. A similar pattern was observed with the bursting pressure. In contrast, gelatinase activity (MMP-2 and MMP-9 expression) was significantly higher in the control group on postoperative d 3. On d 3, expression of NF-κB activity was up-regulated in the anastomotic area. Both parthenolide and resveratrol completely attenuated NF-κB activity. Study groups also developed more marked inflammatory cell infiltration and collagen deposition on histology analysis. Parthenolide and resveratrol significantly improved healing and mechanical stability of colonic anastomoses in rats during the early postoperative period. Both agents may be acting to accelerate the host reparative process as well as to enhance protection of the anastomotic wound bed.

Early Postoperative Oral Intake Accelerates Upper Gastrointestinal Anastomotic Healing in the Rat Model

In our previous study, we reported that early postoperative oral feeding accelerated upper gastrointestinal anastomotic healing in rats. To investigate its underlying mechanism, we performed in vivo and in vitro experiments. Rats that received proximal jejunal anastomosis were divided into four groups: the enteral nutrition (EN) group were fed via gastrostomy, the total parental nutrition (TPN alone) group were fed via a venous catheter, the TPN + saline group received an additional administration of normal saline solution via gastrostomy, and the TPN + water group received an additional administration of distilled water via gastrostomy. The anastomotic bursting pressure (ABP) and the hydroxyproline content of the anastomotic tissue were measured 5 d postoperatively. In an in vitro setting, the rat gastrointestinal fibroblasts were subjected to uniaxial stretching for 60 min, and the expression of type I and type III collagen mRNA was evaluated. The ABP and hydroxyproline content in the EN group, the TPN + saline group, and the TPN + water group were significantly higher than those in the TPN alone group (ABP; 214.6 ± 42, 199.4 ± 36, and 187.3 ± 29 versus 149.5 ± 49 mmHg; P < 0.01, hydroxyproline; 63.5 ± 10, 67.8 ± 13, and 64.1 ± 14 versus 50.5 ± 12 μmol/g dry tissue; P < 0.01). The mRNA levels of type I and type III collagen were increased by stretch stimulation. These results suggest that mechanical loading plays a key role in anastomotic healing. Further investigations are necessary to confirm this suggestion.

Insulin-like growth factor 1-coated sutures improve anastomotic healing in an experimental model of colitis

: Exogenously applied insulin-like growth factor (rhIGF-1) may improve normal intestinal healing. This study examined the effect of rhIGF-1-coated sutures on anastomotic healing in experimental colitis. : Acute colitis was induced in rats by dextran sodium sulphate (DSS). Inflammation was assessed by clinical Disease Activity Index (DAI), myeloperoxidase (MPO) measurement and histological examination. A distal colonic anastomosis was performed using sutures coated with rhIGF-1 dissolved in poly(D,L-lactide) (PDLLA) under general anaesthetic. Anastomotic healing was evaluated histologically, and by hydroxyproline measurement and bursting parameters after 1, 3 and 7 days, and compared with healthy, DSS and DSS + PDLLA controls. : DAI, MPO and histological inflammation scores were significantly increased in all animals treated with DSS. Bursting occurred less often within the anastomotic line on day 3 in the IGF group than in DSS controls (three versus eight of ten). On day 7, the IGF group had significantly increased histological healing scores (mean(s.e.m.) 12.5(0.7) versus 9.2(0.8) (P < 0.050)) and hydroxyproline content (4.6(0.3) versus 3.6(0.1) mg/g tissue; P < 0.050) compared with DSS controls. : IGF-1-coated sutures improve important aspects of anastomotic healing in rats with experimental colitis.

Effect of honey versus intergel in intraperitoneal adhesion prevention and colonic anastomotic healing: A randomized controlled study in rats

Introduction Intra-abdominal adhesion formation and reformation after surgery are still an unavoidable event in spite of modern surgical techniques and are a cause of significant morbidity, resulting in infertility, pain and intestinal obstruction. Aim To investigate the effect of honey in adhesion prevention and colonic anastomotic healing in rats. Methods In the present study, 75 male Sprague–Dawley rats were used and divided into 3 groups for study: [25 rats for each], the intergel, honey and control groups. After the scheduled two-week's post-operative period, all survived rats were reopened for second-look laparotomy to detect the following parameters: a – adhesion, b – manometric study, c – histopathological study. Results The author found that the total adhesion score, the manometric values and the histopathological study among the three studied groups showed statistically significant difference and in favor of the honey-treated rats. Conclusion Honey surpasses the intergel for the healing power and adhesion prevention.

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

To the Editor, We read with great interest the article by Uzun et al. [1], whose work shows that sildenafil citrate therapy might improve anastomotic healing by its effect on nitric oxide (NO) and oxidative stress metabolism. We would like to expand on this concept by introducing a major route by which sildenafil citrate could potantiate platelet inhibition and improve microcirculation. Phosphodiesterase-5 (PDE-5) inhibitors prevent the breakdown of nitric oxide–derived cGMP, primarily in vascular smooth muscle cells, and they thus cause vasodilation. Several investigators have shown that mucosal injury to the gastrointestinal system may be caused by platelet activating factor (PAF), which is known for its vasoactive properties; in the mesenteric region, PAF causes vasoconstriction and tissue hypoperfusion, which may lead to gastrointestinal mucosal ulceration [2, 3]. Platelets have also been well studied with respect to PDEs, and cGMPdependet protein kinase has been shown to play an important role in platelet inhibition by NO. Hart et al. [4] have reported that sildenafil therapy significantly improved postoperative skin flap viability by improving microcirculation and platelet inhibition. In a recent study we found that sildenafil reduced the degree of ischemic intestinal mucosal damage by its effects on the vascular smooth muscle and the microcirculatory hemodynamics related to platelet function [5]. This important mechanism should be borne in mind, as it may be of interest in examining the potential benefical effects of this drug in a model of acute mesenteric ischemia with nonocclusive vasospastic diseases.

Adipose-derived mesenchymal stem cells in biosutures do not improve healing of experimental colonic anastomoses

The feasibility of producing 'biosutures' coated with adipose-derived mesenchymal stem cells (ASCs) was assessed and their effect on colonic anastomoses evaluated. Sutures were cultured with ASCs isolated from BDIX rats before analysis by light and scanning electron microscopy. Anastomoses were performed in 40 BDIX rats using either biosutures or conventional sutures. Histopathological features, adhesion formation and anastomotic strength were evaluated. Sutures were coated with ASCs within 24 h. Anastomoses made with biosutures had a lower adhesion index only during the first week (P = 0.006 at 7 days), but not subsequently. There were no significant differences in anastomotic healing with the two types of suture. ASC biosutures have no effect on anastomotic healing in rats.

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.