Does Low Molecular Weight Heparin Impair Anastomotic Wound Healing?

Background  Enoxaparin is an important molecule which had been using in prophylaxis and treatment of deep venous thrombosis. Also, it is showed that it prevents postsurgical peritoneal adhesions in rats. It is aimed to evaluate its effects on gastrointestinal wound healing. Methods  Thirty Wistar albino rats were divided into three groups as control, subcutan, and intraperitoneal enoxaparin groups. Left colon anastomoses were performed. On postoperative seventh day, anastomotic healing was evaluated by measuring anastomotic bursting pressure, tissue hydroxyproline levels, and histopathological examination. Results  The anastomotic bursting pressure was highest in subcutan enoxaparin group (p < 0.001), intraperitoneal enoxaparin group (p < 0.01) came the second, and the control group has the worst value. The hydroxyproline results were found nearly similar to the bursting pressure values (subcutan (p < 0.001) > intraperitoneal (p < 0.05) > control). Neovascularization in subcutan group (p < 0.001) has a statistically significant difference to other groups. Conclusion  Enoxaparin did not interfere with colonic anastomotic resistance but improved the intestinal wound healing.     

The Effects of Simvastatin on Ischemia Reperfusion Injury in an Experimental Colon Anastomosis Model

Anastomotic leakage is more frequently reported in colonic anastomoses. Ischemia reperfusion injury is one of the main reasons for anastomotic leakage. Simvastatin is known to prevent tissue damage induced by free oxygen radicals after ischemia reperfusion injury. The effect of simvastatin on colonic anastomosis impaired by ischemia reperfusion injury is investigated. Single layer, end-to-end colocolic anastomosis after 0.5-cm colon resection was performed in Wistar Albino rats. In Group 1 (control) (n?=?10), colonic anastomosis without I-R was performed. In Group 2 (n?=?10), the superior mesenteric artery was clamped for 10 min followed by 60 min of reperfusion after which resection anastomosis was performed. In Group 3 (n?=?10), 10 mg/kg simvastatin was given by gavage for 7 days after I-R and resection anastomosis. In Group 4 (n?=?10), the rats received 10 mg/kg simvastatin by gavage 7 days before and 7 days after ischemia reperfusion and surgery. All of the rats were sacrificed 8 days after surgery. Anastomotic bursting pressure and tissue hydroxyproline levels were measured. Postoperative administration of simvastatin restored the anastomotic bursting pressure and hydroxyproline levels to that of control group thus overcoming the effect of ischemia reperfusion injury. Simvastatin administered postoperatively in an experimental model of colonic resection anastomosis impaired by ischemia reperfusion injury increased anastomotic bursting pressures and tissue hydroxyproline levels. Further experimental and clinical studies will show whether administration of simvastatin will increase reliability of the anastomosis and decrease postoperative morbidity and mortality in colonic anastomosis after ischemia reperfusion injury.     

Effect of Peritoneal Lavage with Taurolidine on Primary Colonic Anastomosis in a Rat Model of Secondary Peritonitis

Purpose The reported antibacterial, antiendotoxic, and antiadhesive effects of taurolidine prompted us to study the benefits of intraperitoneal lavage with taurolidine on primary colonic anastomosis in a rat model of secondary peritonitis. Methods We induced peritonitis in 40 rats by injecting Escherichia coli isolate intraperitoneally. We performed colonic resection and primary anastomosis 5 h later, after lavage with either taurolidine or saline solution. After the rats were killed, on postoperative day (POD) 3 (n = 10) or 7 (n = 10), we measured the bursting pressures and hydroxyproline levels, then examined the resected specimens histologically. Results Bursting pressures and tissue hydroxyproline levels were significantly higher in the taurolidine group than in the control group on PODs 3 and 7 (P < 0.05). Histopathological examination revealed significantly higher fibroblastic activity in the taurolidine group. Conclusions The higher bursting pressures and tissue hydroxyproline levels in the rats given taurolidine showed the positive effect of taurolidine on anastomotic strength in secondary peritonitis. Taurolidine is a novel antibiotic with both antibacterial and antiendotoxic effects. Intraperitoneal lavage with taurolidine solution may reduce the risks associated with performing primary colonic anastomosis in patients with secondary peritonitis.     

The Effects of Resveratrol on the Healing of Left Colonic Anastomosis

Introduction: Resveratrol (RSV) is a natural polyphenolic compound found in grape skins and the red wine which improves histological reorganization of the regenerating tissue in dermal wound healing. Since anastomotic healing possesses paramount importance to prevent complications in colorectal surgery, the present study is aimed to evaluate the effect of RSV on the healing of experimental left colonic anastomoses. Methods: Thirty-two male Wistar albino rats were randomized into two groups and subjected to colonic anastomosis. The study group was treated with RSV and the control group received tap water instead. The rats were sacrificed 3 and 7 days postoperatively. Wound complications, intra-abdominal abscesses, and anastomotic leaks and stenosis were recorded. Four types of assessment were performed: bursting pressure, hydroxyproline (OHP) content, histopathology, and biochemical analysis. Results: Compared to the control group, the RSV-treated rats displayed a higher bursting pressure (p <. 001) and anastomotic OHP content (p <. 05)]. RSV treatment leads to significant increase in PON activity at both time points and decrease in malondialdehyde levels on postoperative day 3 (p <. 001). Histopathological analysis revealed that RSV administration leads to a better anastomotic healing in terms of mucosal ischemia, neovascularization, reepithelialization, fibroblast, and lymphocyte infiltration. Conclusion: The study results suggest that exogenous RSV administration exerts a positive effect on experimental colonic wound healing in the rat. Although the precise cellular mechanisms by which RSV enhances anastomotic wound healing is not clear, stimulation of neovascularization, generation of collagen synthesis, inhibition of overinflammation, and restriction of oxidative injury seems to be of paramount importance.     

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

Background The benefits of early postoperative oral feeding following colonic anastomosis have previously been demonstrated. However, early postoperative oral feeding in patients with upper gastrointestinal surgery has been avoided because of concerns regarding anastomotic leakage. We investigated whether early postoperative oral feeding was advantageous for upper gastrointestinal anastomosis in comparison to parenteral feeding with a fasting period. Materials and Methods Male Sprague-Dawley rats were subjected to the same surgical manipulation, i.e., venous catheterization, gastrostomy, and proximal jejunal anastomosis. Rats were divided into two groups: the enteral nutrition (EN) group, which received nutrients via gastrostomy as a substitute for oral feeding, and the total parental nutrition (TPN) group, which was fed via a venous catheter. Identical nutritional solutions were administered to the two groups immediately after surgery. The anastomotic bursting pressure (ABP) and the content of hydroxyproline in the anastomotic tissue were measured 5 days postoperatively. Results The ABP in the EN group was significantly higher than that in the TPN group (214.6 ± 42 versus 149.5 ± 49 mmHg; p < 0.01). The hydroxyproline content in the EN group was also significantly higher (63.5 ± 10 versus 50.5 ± 12 μmol/g dry tissue; p < 0.01). Conclusions Early enteral feeding via gastrostomy accelerated jejunal anastomotic healing in comparison to parenteral feeding. This study clearly indicates that early oral feeding after upper gastrointestinal surgery leads to prompt anastomotic healing.     

Role of Activated Protein C on Wound Healing Process in Left Colonic Anastomoses in the Presence of Intra-abdominal Sepsis Induced by Cecal Ligation and Puncture: An Experimental Study in the Rat

Background  Activated protein C (APC) is a serine protease with anticoagulant and anti-inflammatory activities. The delaying effects of intra-abdominal sepsis on wound healing process in colonic anastomoses have been previously demonstrated. This study was designed to investigate the role of APC on wound healing process in left colonic anastomoses in the presence of intra-abdominal sepsis. Methods  The left colonic anastomosis was performed in 48 rats that were divided into four groups: (1) sham-operated group, laparatomy plus cecal mobilization (n = 12); (2) sham + APC group, identical to group I except for APC treatment (n = 12); (3) CLP group, cecal ligation and puncture (n = 12); 4) CLP + APC-treated group, 100 μg/kg, 15 min before the construction of colonic anastomosis (n = 12). Anastomotic bursting pressures were measured in vivo on day 7. Tissue samples were obtained for analyses of hydroxyproline (HP) contents, myeloperoxidase (MPO) acivity, malondialdehyde (MDA), and nitrate/nitrite (NO₃⁻/NO₂⁻) levels. The plasma levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, and D-dimer also were measured. Results  Intra-abdominal sepsis led to significant decreases in colonic anastomotic bursting pressures and tissue HP contents, along with increases in MPO activity, MDA and NO₃⁻/NO₂⁻ levels, and also plasma levels of TNF-α, IL-6, and D-dimer (P < 0.05). However, APC treatment led to significant increases in anastomotic bursting pressures and tissue HP ontents, along with decreases in MPO activity, MDA and NO₃⁻/NO₂⁻ levels, and also plasma levels of TNF-α, IL-6, and D-dimer (P < 0.05). Conclusions  This study clearly showed that APC treatment prevented the delaying effects of intra-abdominal sepsis on colonic anastomotic wound healing process. Further clinical studies are required to determine whether APC has a useful role in the enhancement of anastomotic healing during particular surgeries in which sepsis-induced injury occurs.     

The Effects of Hyperbaric Oxygen Therapy on Colonic Anastomosis in Rats With Peritonitis

The aim of this study is to investigate the healing effect of hyperbaric oxygen (HBO) on colonic anastomoses in the presence of experimentally induced peritonitis. Thirty-two rats were allocated randomly into short-term anastomosis (STA), short-term anastomosis + HBO treatment (STA+HBO), long-term anastomosis (LTA), and long-term anastomosis + HBO (LTA+HBO) treatment groups. The STA and LTA groups were administered fluid resuscitation and antibiotics for 3 and 7 days, respectively, whereas the HBO treatment groups received additional HBO therapy for 3 and 7 days, respectively. The rats were reoperated on the third and the seventh days of anostomoses for evaluation. The bursting pressures in STA+HBO and LTA+HBO therapy groups were significantly higher than those in groups with anastomoses alone (p <. 001 and p <. 01). HBO therapy did not affect the fibrotic index neither in STA nor in LTA groups (p >. 05 for both); however, it was significantly higher in LTA+HBO group than that in STA+HBO group (p <. 05). The hydroxyproline level was significantly higher in LTA group than in STA group (p <. 05), yet HBO therapy did not affect the hydroxyproline levels in STA or LTA groups (p >. 05 for both). It is concluded that hyperbaric oxygen treatment has positive effects on colonic anastomotic healing in case of peritonitis.     

Pyrrolidine Dithiocarbamate Prevents Deleterious Effects of Remote Ischemia/Reperfusion Injury on Healing of Colonic Anastomoses in Rats

Background Pyrrolidine dithiocarbamate (PDTC) is a low-molecular-weight thiol antioxidant and potent inhibitor of nuclear factor-κB (NF-κB) activation. It has been shown to attenuate local harmful effects of ischemia/reperfusion (I/R) injury in many organs. In recent animal studies, a delaying effect of remote organ I/R injury on the healing of colonic anastomoses has been demonstrated. In this study we investigated whether PDTC prevents harmful systemic effects of superior mesenteric I/R on left colonic anastomosis in rats. Methods Anastomosis of the left colon was performed in 40 rats randomly allocated into the following four groups: (1) Sham-operated group (group I, n = 10)—simultaneously with colonic anastomosis, the superior mesenteric artery and collateral branches divided from the celiac axis and the inferior mesenteric artery were isolated but not occluded. (2) Sham+PDTC group (group II, n = 10)—identical to sham-operated rats except for the administration of PDTC (100 mg/kg IV bolus) 30 minutes prior to commencing the experimental period. (3) I/R group (group III, n = 10)—60 minutes of intestinal I/R by superior mesenteric artery occlusion. (4) PDTC-treated group (group IV, n = 10)—PDTC 100 mg/kg before and after the I/R. On postoperative day 6, all animals were sacrificed, and anastomotic bursting pressures were measured in vivo. Tissue samples were obtained for investigation of anastomotic hydroxyproline (HP) contents, perianastomotic malondialdehyde (MDA) levels, myeloperoxidase activity (MPO), and glutathione (GSH) level. Results There was a statistically significant decrease in anastomotic bursting pressure values, tissue HP content and GSH level, along with an increase in MDA level and MPO activity in group III, when compared to groups I, II, and IV (p < 0.05). However, PDTC treatment led to a statistically significant increase in anastomotic bursting pressure values, tissue HP content and GSH level, along with a decrease in MDA level and MPO activity in group IV (p < 0.05). Conclusions This study showed that PDTC treatment significantly prevented the delaying effect of remote organ I/R injury on anastomotic healing in the colon. Further clinical studies are needed to clarify whether PDTC may be a useful therapeutic agent for increasing the safety of the anastomosis during particular operations where remote organ I/R injury occurs.     

The Effect of Purified Micronized Flavonoid Fraction on the Healing of Anastomoses in the Colon in Rats

Purpose Anastomotic leakage of colonic and rectal anastomoses is a major complication after large intestine surgery. Many factors influence the healing of colon anastomoses. Flavonoids have been recognized for centuries as physiologically active constituents that are used to treat human diseases. We studied the effects of a clinically used, micronized, purified flavonoid fraction on the healing of colonic anastomosis in rats. Methods Male Sprague–Dawley rats were used. The flavonoid group of rats received 100 mg/kg per day of Daflon for 14 days until surgery. Thereafter, a resection and anastomosis were performed. The bursting pressure of the anastomoses and the hydroxyproline levels of the perianastomotic tissue were determined to evaluate the healing on the third and seventh days of surgery for both flavonoid and control groups. Results The bursting pressure of the flavonoid group was higher on the seventh day. The hydroxyproline levels of the flavonoid group were significantly higher than in the control group on both the third and seventh days after surgery. Conclusions Although the micronized purified flavonoid fraction has some inhibitory properties on the healing of the anastomosis, its net effect was to obtain a better anastomotic healing of the colon in rats.     

The Effect of Erythropoietin on Anastomotic Healing of Irradiated Rats

ABSTRACT

Aim: The aim of the present study is to evaluate the possible protective effects of erythropoietin (EPO) on anastomotic wound healing after preoperative radiotherapy according to its pleiotropic mechanism of action. Methods: Thirty-two male Wistar albino rats were randomized into four groups containing eight rats each: ANAS group, standard resection plus anastomosis; RT+ANAS group, radiation plus standard resection plus anastomosis; ANAS+EPO group, standard resection plus anastomosis plus EPO; RT+ANAS+EPO, radiation plus standard resection plus anastomosis plus EPO. All animals were sacrificed by cardiac puncture, and anastomotic healing was measured by bursting pressure, hydroxyproline (OHP) levels, myeloperoxidase (MPO) activity and histopathological evaluations. Malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9) were also measured in serum specimens. Results: OHP levels in the RT+ANAS + EPO group were significantly increased compared with other groups (p < .05). In contrast, MPO activity in the RT+ANAS+EPO group was significantly decreased compared with other groups (p < .05). Serum MDA levels were found to be decreased in the ANAS+EPO and RT+ANAS+EPO groups (p < .05). Group comparisons demonstrated that bursting pressure was significantly higher in EPO treated rats (p < .05). The histopathology results revealed that EPO treatment improves anastomotic wound healing though decreased necrosis and inflammatory cell infiltration and increased fibroblast activity. Conclusion: The findings of the present study indicate that EPO contributes to wound healing and the strength of colon anastomosis following radiation due to its antioxidant and anti-inflammatory effects, but further studies are needed to explore the significance of these effects.     

The Effect of Platelet-Rich-Plasma on the Healing of Left Colonic Anastomosis in a Rat Model of Intra-Abdominal Sepsis

Objective: The aim of this study was to investigate the effect of platelet-rich plasma (PRP) on the healing of colonic anastomosis in the presence of sepsis. Materials and Method: Fifty Wistar-albino male rats were used. Ten healthy rats were euthanized to prepare PRP, the rest were subjected to colonic anastomosis and randomly allocated into four groups of 10 rats each as anastomosis without PRP (C), without PRP in sepsis (SC), anastomosis with PRP (C-PRP), and with PRP in sepsis (S-PRP). Sepsis was induced by cecal ligation and puncture procedure. All animals were euthanized on postoperative day 7. The body weight change, anastomotic bursting pressure (ABP), tissue hydroxyproline (TH) and histopathological examination of each group were analyzed by using one-way analysis of variance (ANOWA) and Tukey's HSD post-hoc test to assess the differences between the groups. Results: There was no statistical difference among the groups in terms of body weight changes. The ABP was measured at a mean value of 179.5 ± 10.3, 129.3 ± 14.2, 209 ± 14.4, and 167.5 ± 7.5 mm-Hg, in group C, SC, C-PRP, and S-PRP, respectively. The ABP and TH of C-PRP group was significantly higher than three groups (p < .05, for each comparison). In sepsis, PRP significantly raised the mean ABP and TH levels up to the levels of C group. Tissue regeneration was significant with increased collagen formation in C-PRP group than the other groups (p < .05). The healing effect of PRP in the presence of sepsis was significant than S-group (p < .05), while similar to C group (p = .181). Conclusion: PRP application to colonic anastomosis promotes the healing process in rats with intra-abdominal sepsis.     

Early Anastomotic Repair in the Rat Intestine is Affected by Transient Preoperative Mesenteric Ischemia

Introduction  During bowel surgery, perioperative blood loss and hypotension can lead to transient intestinal ischemia. Recent preclinical studies reveal that the strength of intestinal anastomoses can be compromised after reperfusion. So far, this phenomenon has not been investigated in the very first days of healing when wound strength is lowest. Material and Method  Ischemia was induced in rats by clamping both the superior mesenteric artery and ileal branches for 30 min. Immediately after declamping, anastomoses were constructed in both terminal ileum and descending colon. The same was done in control groups after sham-ischemia. Anastomotic bursting pressure and breaking strength were measured immediately after operation (day 0) and after 1, 2, or 3 days. Anastomotic hydroxyproline content, gelatinase activity, and histology were analyzed. Results and Discussion  In ileal anastomoses, at day 1, both the breaking strength and bursting pressure were significantly (p < 0.05) lower in the ischemic group, while at day 2, this was the case for the bursting pressure only. In the colon, the bursting pressure in the ischemic group was lower at day 1. Anastomotic hydroxyproline content remained unchanged. Increased presence of the various gelatinase activities was found in ileum only at day 0 and in colon at days 1 and 2. Histological mucosal damage was found in ischemia–reperfusion groups. Conclusion  Transient mesenteric ischemia can negatively affect anastomotic strength during the very first days of healing, even if the tissue used for anastomotic construction looks vital.     

Effects of pneumoperitoneum with or without colostomy on rat colonic anastomotic healing

Background: Elevated intra‐abdominal pressure and colostomy have adverse effects on colonic anastomoses. The aim of the present study was to investigate the effects of laparoscopic colon surgery with and without diverting colostomy on healing of colonic anastomoses in an experimental model. Methods: Thirty‐six male rats were divided into three equal groups: group 1, control (colonic anastomosis and anaesthesia for 180 min only); group 2, 180 min pneumoperitoneum and colonic anastomosis; and group 3, similar to group 2 with a proximal colostomy. On day 7, bursting pressures, tissue hydroxyproline and nitric oxide concentrations and histopathological inflammation scores were determined and compared. Results: Mean bursting pressures were higher in the control group than the two pneumoperitoneum groups (P = 0.0003). Mean tissue hydroxyproline concentrations showed no difference (P > 0.05). Mean tissue nitric oxide concentrations were significantly increased in the control group (P = 0.0013). Histopathological scores demonstrated increased inflammatory response in group 3 compared to the controls (P = 0.0009). Conclusion: Pneumoperitoneum delays collagen maturation and impairs anastomotic strength in the colon. Following pneumoperitoneum, performance of a diverting loop colostomy to protect the anastomosis will not have additional detrimental effects on anastomotic healing.     

The effect of calcitonin gene-related peptide on healing of intestinal anastomosis in rats with experimental obstructive jaundice

Purpose  Intestinal anastomotic healing is a complex procedure in which several mediators and cytokines play roles. Calcitonin gene-related peptide is an important neuropeptide in inflammation. In this study we aimed to investigate the effect of calcitonin gene-related peptide on healing of intestinal anastomosis in rats with obstructive jaundice. Materials and methods  Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Four days after the operation, intestinal anastomosis was performed, and either calcitonin gene-related peptide or 0.9% NaCl was administered intraperitoneally to these jaundiced rats and controls. The concentrations of serum tumor necrosis factor-α (TNF-α) and triglyceride levels of all rats were measured, and healing of the anastomosis was evaluated by measuring the bursting pressure and hydroxyproline content on the 7th postoperative day. Results  Calcitonin gene-related peptide was found to have positive effects on healing of the anastomosis by inhibiting the effects of TNF-α and increasing the bursting pressure and hydroxyproline content of the anastomosis. Conclusion  Calcitonin gene-related peptide increases anastomotic wound healing in experimental anastomosis in the presence of obstructive jaundice in rats.     

Effect of matrix metalloproteinase inhibition on colonic anastomotic healing in rats

Wound strength depends on the balance between collagen synthesis and degradation; however, the role of collagen breakdown in wound healing is still not well understood. We investigated the role of matrix metalloproteinases in wound healing by using BE16627B, a matrix metalloproteinase inhibitor. Identical surgical procedures consisting of a colonic anastomosis (single-layer, inverted) and implantation of an osmotic pump in the back were performed in male Sprague-Dawley rats weighing 270 to 290 grams. The animals were randomly assigned to receive either BE16627B (n = 10) dissolved in dimethylsulfoxide and diluted with ethylene glycol at a dosage of 2.4 mg/rat/day for 3 days or the vehicle solution alone (n = 11). The solutions were administered through the surgically implanted osmotic pumps. The animals were killed 4 days after surgery, and the colonic bursting pressure (mm Hg) and hydroxyproline concentration (μg/mg wet tissue, index of collagen) were measured. The administration of BE16627B enhanced colonic anastomotic healing, as measured by the increase in the colonic bursting pressure (160 ±12 vs. 125 ±7 mm Hg; P <0.05) and the increase in the soluble fraction of collagen (0.27 ± 0.01 vs. 0.21 ± 0.01 μg/mg wet tissue; P <0.01) in the anastomosis. Histologic examination of the tissue revealed that the use of BE 1662 7B resulted in the preservation of the multilayered colonic structure and increased the network of collagen between both ends of the colon in the thickening submucosal layer. These findings demonstrate that the inhibition of matrix metalloproteinase activity influences colonic anastomotic healing, indicating a potential mechanism for enhancing anastomotic healing. Supported by a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science. Presented at the Forty-First Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif., May 21–24, 2000.     

Is Synchronous Bowel Anastomosis Safe ?

In this study, we investigated the effects of synchronous anastomosis on intestinal healing in experimental colonic resection. Sprague-Dawley rats were randomized into 3 groups; control (group I), single anastomosis (group II) and synchronous (double) anastomosis (group III). Single and proximal anastomoses were located 3 cm distal to caecum, and distal anastomoses were done 3 cm distal to them. On the 7^th postoperative day, bursting pressure, hydroxy-proline level and histology of the anastomotic site were assessed. Bursting pressures and hydroxyproline levels indicated that impaired healing of proximal anastomoses in group III was evident. Proximal anastomoses in group III had the lowest hydroxyproline value and bursting pressure level. Significant fibrosis was observed in the histological examination of distal anastomoses in group III. Double colonic anastomoses is not as safe as single anastomoses and involves additional risk. The healing of proximal anastomosis is significantly altered after experimental synchronous resection.     

Effect of supplemental vitamin A on the healing of colon anastomosis

The effect of dietary supplementation with vitamin A on the healing of colon anastomoses was studied. Fifty adult male Sprague-Dawley rats were divided into two groups: (1) rats fed a standard chow which contains the equivalent of about 15 IU vitamin A/g diet; (2) rats fed the chow supplemented with an additional 150 IU vitamin A/g diet. Rats were prefed for 5 days; on Day 6 under ether anesthesia the colon was divided 1-in. distal to the ileocecal junction and then reanastomosed. The rats were maintained on the above diets for 5 days and killed on the sixth postoperative day with ether and the segment of colon containing the anastomosis was resected. In 15 rats of each group, the breaking strength of the anastomosis was measured. In the remaining 10 rats of each group, the bursting strength of the anastomotic site and a segment of normal distal colon was measured. Samples of colon from the anastomotic site and the normal segment were analyzed for hydroxyproline. There was a significant decrease in hydroxyproline content at the anastomotic site when compared to the normal distal colon segment in each group of rats (P < 0.01). The hydroxyproline content of both normal colon and the anastomotic site was significantly higher in the vitamin A-supplemented rats than in the control diet rats (P < 0.01). There was also a significant increase in bursting strength in the vitamin A-supplemented rats both of the anastomotic site (P < 0.01) and of the normal colon segment (P < 0.01). The anastomotic breaking strength peak values did not differ significantly between the two groups, but the area under the breaking strength curve (an expression of the energy required to break the anastomosis) was three times greater in the vitamin A-supplemented rats than in the controls (P < 0.001). It is concluded that vitamin A supplementation has a beneficial effect on the healing of colon anastomoses in rats.     

The effect of intraoperative colonic lavage withN G -nitro-l-arginine methyl ester (l-NAME) on anastomotic healing in the presence of left-sided colonic obstruction in the rat

-arginine methyl ester (L-NAME) on the healing of colonic anastomosis in the presence of a left-sided obstruction in the rat was investigated. Left-sided colonic obstruction was created in 144 Wistar rats. The obstruction site was excised 24 h later and anastomosis was performed after either no irrigation or colonic lavage with either saline, povidone iodine (PI), short-chain fatty acids (SCFA), L-NAME, or glutamine, in 24 animals each. Animals were killed on days 3 and 6, and a 4-cm colonic segment with the anastomosis at the center was excised. Bursting pressure (BP) and hydroxyproline (HP) content were measured. In the saline, PI, and SCFA groups, BP was higher (P < 0.05, P < 0.05, and P < 0.001, respectively) and HP concentration was similar compared with controls. Both the BP and HP concentrations were higher in the glutamine group compared with controls (P < 0.001). BP was lower (P < 0.05) and HP concentration was similar in the L-NAME group compared with the control group. Colonocyte nutrition and tissue perfusion are the mainstays of anastomotic healing. Intraoperative colonic lavage with L-NAME suppresses colonic anastomotic healing in the presence of a left-sided obstruction. (Received for publication on Mar. 29, 1999; accepted on Nov. 11, 1999)     

Effects of Pyrrolidine Dithiocarbamate on Healing of Colonic Anastomoses in the Cecal Ligation and Puncture Model of Intraperitoneal Sepsis in Rats

Introduction Pyrrolidine dithiocarbamate (PDTC) is a low-molecular thiol antioxidant and potent inhibitor of nuclear factor-κB (NF-κB) activation. In recent animal studies, the delaying effect of intraperitoneal sepsis on healing of colonic anastomoses has been demonstrated. In this study, we aimed to investigate the effects of PDTC on healing of colonic anastomoses in the presence of intraperitoneal sepsis induced by a rodent model of cecal ligation and puncture (CLP). Methods Anastomosis of the left colon was performed on the day following CLP in 30 rats that were divided into three groups: sham-operated control (laparotomy and cecal mobilization, group I, n =10), cecal ligation and puncture (CLP) (group II, n = 10), PDTC-treated group (100 mg/kg IV before construction of the colonic anastomosis) (group III, n = 10). On postoperative day 6, all animals were sacrificed, and anastomotic bursting pressures were measured in vivo. Tissue samples were obtained for further investigation of colonic anastomotic hydroxyproline (HP) contents, perianastomotic myeloperoxidase (MPO) activity, and malondialdehyde (MDA) and glutathione (GSH) levels. Results There was a statistically significant increase in the activity of MPO and MDA levels in the CLP group (group II) along with a decrease in GSH levels, colonic anastomotic HP contents, and bursting pressure values when compared to controls (group I). However, PDTC treatment led to a statistically significant increase in the tissue HP contents, GSH levels, and colonic anastomotic bursting pressure values, along with a decrease in MPO activity and MDA levels in group III (p < 0.05). Conclusions This study showed that PDTC treatment significantly prevented the delaying effect of CLP-induced intraperitoneal sepsis on anastomotic healing in the colon. Further clinical studies are needed to clarify whether PDTC may be a useful therapeutic agent to increase the safety of the anastomosis during particular operations where sepsis-induced injury occurs.