Anastomotic Breaking Strength Research Articles

Glucagon-Like Peptide-2 Analogue ZP1849 Augments Colonic Anastomotic Wound Healing

Background The enteroendocrine hormone glucagon-like peptide- (GLP-) 2 is a potent trophic factor in the gastrointestinal tract. The GLP-2 receptor (GLP-2R) is expressed in the stroma of the large bowel wall, which is the major therapeutic target area to prevent anastomotic leakage. We investigated the efficacy of the long-acting GLP-2 analogue ZP1849 on colonic anastomotic wound healing. Methods Eighty-seven male Wistar rats were stratified into four groups and received daily treatment with vehicle or ZP1849 starting one day before (day -1) end-to-end anastomosis was constructed in the left colon on day 0, and on days 0 (resected colon segment), 3, and 5, gene expressions of GLP-2R, Ki67, insulin-like growth factor- (IGF-) 1, type I (COL1A1) and type III (COL3A1) procollagens, cyclooxygenase- (COX-) 1, COX-2, and matrix metalloproteinase- (MMP-) 7 were quantified by RT-qPCR. Breaking strength, myeloperoxidase (MPO), transforming growth factor- (TGF-) β1, and soluble collagen proteins were measured on days 3 and 5. Results ZP1849 treatment increased Ki67 (P < 0.0001) and IGF-1 (P < 0.05) mRNA levels in noninjured colon day 0, and postoperatively in the anastomotic wounds compared to vehicle-treated rats. ZP1849-treated rats had increased (P = 0.042) anastomotic breaking strength at day 5 compared with vehicle. COL1A1 and COL3A1 mRNA levels (P < 0.0001) and soluble collagen proteins (P < 0.05) increased from day 3 to day 5 in ZP1849-treated rats, but not in vehicle-treated rats. COX-2 mRNA and MPO protein levels decreased from day 3 to day 5 (P < 0.001) in both groups. ZP1849 treatment reduced TGF-β1 protein levels on day 5 (P < 0.001) but did not impact MMP-7 transcription. Conclusions The GLP-2 analogue ZP1849 increased breaking strength, IGF-1 expression, and cell proliferation, which may be beneficial for colonic anastomotic wound healing.

The effect of gender on early colonic anastomotic wound healing.

Clinically, male patients subjected to colorectal surgery are more prone to develop anastomotic leakage than female patients by unknown mechanisms. Our aim was to investigate the impact of gender on anastomotic wound healing using an experimental model. One-layer colonic anastomosis was constructed in 8-week-old 28 male and 32 female Sprague-Dawley rats. Animals of one group (n = 30) were sacrificed immediately after surgery day 0 and the other group (n = 30) on postoperative day 3. Anastomotic breaking strength, total collagen (hydroxyproline), soluble collagen (Sircol), matrix metalloproteinase (MMP)-9, and transforming growth factor (TGF)-β1 were measured. The anastomotic breaking strength decreased from day 0 to day 3 with no significant gender differences either in the extent of decline (P = 0.122) or absolute day 3 strengths (P = 0.425). Analogously, total collagen concentration in the anastomotic wounds decreased postoperatively and were lower (P = 0.043) in the male compared with the female rats on day 3. MMP-9 levels increased in the anastomoses postoperatively, but they did not differ (P = 0.391) between male and female animals. Soluble collagen levels were lower in the day-3 anastomoses of male versus female rats (P = 0.015) and correlated positively with total TGF-β1 levels (rS = 0.540, P = 0.006). Although TGF-β1 tended to be lower in male compared with the female rats, the differences did not reach statistical significance. Our findings point towards a less favorable collagen metabolism in colonic anastomoses of male compared with female rats during early wound healing.

Influence of Early Postoperative Feeding in Gastrointestinal Anastomotic Fistula Formation and Healing Time in Rabbits.

Objectives To determine whether early postoperative feeding attenuates the inhibitory effects of intestinal anastomosis in rabbits. Methods After undergoing gastrointestinal anastomosis, 48 rabbits were randomly divided into experimental and control groups. The rabbits in the experimental group were fed a liquid diet beginning 24 h postoperatively, while the control rabbits received only total parenteral nutrition after the operation. Exploratory laparotomies were performed on four rabbits in each group 3, 5, 7, 10, and 15 days postoperatively, and the healing rate of the anastomosis, anastomotic bursting pressure, anastomotic breaking strength, and hydroxyproline content at the anastomosis were determined. Results The anastomoses healed in 91.6% (22/24) of the control group and 95.8% (23/24) of the experimental group. The anastomotic bursting pressure decreased remarkably in both groups 3 days postoperatively, reaching the lowest value. The anastomotic breaking strength did not differ between the two groups 3 days postoperatively, when both reached their lowest points, and both groups increased markedly and peaked 10 days postoperatively. The hydroxyproline content of the anastomosis was slightly lower in the experimental group 3 days postoperatively, although both groups peaked 7 days postoperatively. Conclusions Early postoperative feeding does not increase the anastomosis healing time or rate of gastrointestinal anastomosis leakage.

Selective matrix metalloproteinase inhibition increases breaking strength and reduces anastomotic leakage in experimentally obstructed colon.

Colonic obstruction causes loss of collagen and impairment of anastomotic integrity by matrix metalloproteinases (MMPs). Unexpectedly, pharmacological MMP inhibition increased anastomotic leakage (AL) in obstructed colon possibly due to the non-selective nature of these compounds and the experimental model applied. We therefore studied the effects of selective MMP inhibition on the healing of anastomoses in colon obstructed by a novel laparoscopic technique. Left colon was obstructed in 38 male Sprague-Dawley rats (226-284g). After 12h, stenoses were resected and end-to-end anastomoses constructed. Baseline breaking strength was determined in 6 animals on day 0. The remaining 32 rats were randomized to daily treatment with the selective MMP-8, MMP-9, and MMP-12 inhibitor AZD3342 (n=16) or vehicle (n=16). On day 3, anastomoses were evaluated for AL and breaking strength. Isolated anastomotic wound tissue was analyzed on total collagen and pepsin-insoluble and pepsin-soluble collagen by hydroxyproline. The soluble collagens were further differentiated into native, measured by Sircol, and fragmented forms. Baseline breaking strength was maintained with AZD3342 but decreased by 25% (P=0.023) in the vehicle group. The anastomotic breaking strength of AZD3342-treated rats was 44% higher (P=0.008) than the vehicle-treated rats. Furthermore, the AL rate was reduced (P=0.037) with AZD3342 compared with vehicle treatment. AZD3342 treatment influenced neither the total or insoluble collagen concentrations nor the degree of fragmentation of the soluble collagen triple helices. Selective MMP inhibition increased anastomotic breaking strength and reduced AL after resection of colonic obstruction.

Effect of Postoperative Diclofenac on Anastomotic Strength and Histologic Healing in Rabbit Small Intestine

In this experimental study, we investigated the effects of a 5-day postoperative treatment with the nonsteroidal anti-inflammatory drug (NSAID) diclofenac on anastomotic healing in rabbits. NSAIDs are widely used analgesics in today's “fast-track surgery,” raising concerns about their potential negative effects on healing in humans. A total of 33 New Zealand White female rabbits underwent laparotomy and 2 separate end-to-end anastomoses of the ileum.. The animals were randomized to receive subcutaneous diclofenac 4 mg/kg/d (17 experimental rabbits) or subcutaneous isotonic saline 0.1 mL/kg/d (16 control rabbits) postoperatively. On the fifth postoperative day, the animals were humanely killed, and anastomotic leakage, anastomotic breaking strength, and histopathologic changes were evaluated. Breaking strength in the diclofenac group was 21% lower than in the placebo group (P = 0.027). Anastomotic leakage was found in 4 rabbits in the diclofenac group (26.7%). The rabbits treated with diclofenac demonstrated a 16% lower collagen deposition compared with the placebo group (P = 0.008). In our study, postoperative treatment with diclofenac had a negative effect on the anastomotic healing and strength in the ileum of rabbits. Caution should be taken in the use of diclofenac after gastrointestinal surgery.

Impaired blood supply in the colonic anastomosis in mice compromises healing.

Colon anastomotic leakage has a multifactorial etiology and ischemia is considered one of the most important single factors. However, no existing animal models have established a direct link between ischemia and anastomotic leakage. The aim of this study was to establish a model of colon anastomotic leakage as a result of tissue ischemia. In colon anastomoses of 53 C57BL/6 mice, varying degrees of ischemia were induced. Supplying vessels were divided with bipolar coagulation in order to reduce anastomotic breaking strength and create clinical anastomotic leakage. Breaking strength of all the ischemic anastomoses were significantly lower compared with controls. Increasing ischemia resulted in higher rates of large bowel obstruction without creating anastomotic leakage. Healing was compromised as a result of impaired blood supply. However, clinical leakage was absent. Pure ischemia in otherwise healthy experimental animals may be too simple of an approach to create clinical leakage.

Does acute alcohol intoxication interfere with colonic anastomosis wound healing?: a rat model of nondestructive colon trauma

To evaluate the effects of acute alcohol intoxication on healing of colonic anastomosis. Thirty-six rats were allocated into two groups. Animals in the alcohol (A) were given 2 mL of ethanol diluted in 0.9% saline solution to a concentration of 40% by gavage immediately before anesthesia, whereas control (C) animals received 2 mL of 0.9% saline solution via the same route. A colonic anastomosis was then performed in all animals. On postoperative days 1, 3, and 7, anastomotic breaking strength was assessed and histopathological examination was performed. Change in body weight and mortality were also evaluated. The median of anastomotic tensile strength on the postoperative day 1 was 0.09 Newtons for group A and 0.13 for group C. (p>0.05). The median of anastomotic tensile strength on the postoperative day 3 was 0.13 Newtons for group A and 0.17 for group C. (p>0.05). The median of anastomotic tensile strength on the postoperative day 7 was 0.30 Newtons for group A and 0.35 for group C. (p>0.05). There was no significant difference between the groups A and C, in the first, third or seventh POD (p>0.05), in any of the analyzed parameters. There were no statistical differences between groups in the weight. Three animals died, all from the group A. Acute alcohol intoxication did not interfere with wound healing of colonic anastomoses, although it caused early postoperative mortality.

Expression and inhibition of matrix metalloproteinase (MMP)-8, MMP-9 and MMP-12 in early colonic anastomotic repair

Submucosal collagen is paramount for colonic anastomotic integrity. Matrix metalloproteinases (MMPs) mediate collagen degradation that increases the risk of wound dehiscence. Although broad-spectrum MMP inhibitors are beneficial for anastomotic strength, they can cause adverse reactions. Knowledge of specific MMPs responsible for the weakening of anastomoses can be used to optimise MMP inhibition therapy. We aimed to quantify transcript and protein levels of multiple MMPs in colonic anastomoses and evaluate the effect of inhibiting the MMPs that displayed the highest expression levels on anastomotic repair. Left-sided colonic anastomoses were made in male Sprague-Dawley rats. After 3 days when biomechanical strength is lowest, MMP mRNA and protein levels were measured by quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assays and gelatin zymography. The effects of the MMP-8, MMP-9 and MMP-12 synthetic inhibitor AZD3342 was also studied. MMP-8, MMP-9 and MMP-12 gene and protein expression increased profoundly (p < 0.01), and MMP-13 mRNA and MMP-2 mRNA and protein modestly (p < 0.001) in the anastomoses. MMP-3 mRNA levels were not up-regulated significantly compared with adjacent uninjured colon. Increased anastomotic MMP-12 levels paralleled macrophage infiltration by immunohistochemical analyses. AZD3342 (50 mg/kg) treatment increased the anastomotic breaking strength by 29% (p = 0.015) day 3 compared with vehicle. Improved anastomotic strength was not accompanied with alterations of type I or type III procollagen mRNA but was possibly due to inhibition of the concerted digestive action on the existent submucosal collagens by the targeted MMPs. The present findings justify the concept of selective MMP inhibition to enhance anastomotic strength in colon.

Model of Wound Healing for Esophagogastric Anastomoses in Rats

Background: Anastomotic leakage after esophageal surgery is a significant cause of morbidity and mortality. Postoperative leakage of esophagogastric anastomosis has been reported in 2–30% of surgical patient, resulting in an increased need for reoperation and a high risk of subsequent esophageal stricture formation and fistula. So far, experimental investigations on major factors influencing the healing of esophageal anastomoses, e.g. neovascularization and collagen deposition, have been hindered by the lack of a functional rodent model. Methods: We developed a novel technique of gastric tube formation followed by end-to-end esophagogastric anastomosis in a rat model. Standardized anastomoses were carried out in 18 Brown-Norway rats and normal esophagogastric healing was studied by measuring anastomotic breaking strength 5 days after surgery. Results: Five animals showed an insufficiency of the esophagogastric anastomosis as determined by anastomotic leakage testing. Normal anastomotic healing was found in 10 animals. The anastomotic breaking strength was 1.93 ± 0.45 N. Conclusion: The rat model for performing esophagogastric anastomoses after gastric tube formation may serve as a functional and useful model in future research studies on microvascular and molecular processes of anastomotic healing.

The effect of fibrin glue on the early healing phase of intestinal anastomoses in the rat

PurposeProtecting the anastomotic integrity using suture or staple line reinforcement remains an important goal for ongoing research. The present comprehensive study aims to establish the effects of fibrin glue on the early phase of anastomotic healing in the rat intestine.MethodsOne hundred and eight young adult male Wistar rats underwent resection and anastomosis of both the ileum and colon. In half, fibrin glue was applied around the anastomoses. Parameters for repair included wound strength, both bursting pressure and breaking strength at days 1, 3, and 5 after operation; hydroxyproline content; and histology, the latter also after 7 days.ResultsA transient colonic ileus was observed in the experimental group. Anastomotic breaking strength was always similar in both the control and fibrin glue groups. Anastomotic bursting pressures remained low at days 1 and 3, without any differences between the groups. In both groups, the bursting pressure increased sharply (p < 0.001) between days 3 and 5. At day 5, the bursting pressure in the fibrin glue group remained below than that in the controls, although only significantly (p = 0.0138) so in the ileum. At day 5, but not at day 7, the wounds in the fibrin glue group contained less collagen. Other aspects of microscopic wound architecture appeared to be the same.ConclusionsThere is no justification for using fibrin glue on patent anastomoses constructed under low-risk conditions. Its potential benefit under conditions where chances for anastomotic leakage are enhanced needs further investigation.

Nonselective matrix metalloproteinase but not tumor necrosis factor-α inhibition effectively preserves the early critical colon anastomotic integrity

Increased matrix metalloproteinase (MMP) activity has been implicated in the pathogenesis of colorectal anastomotic leakage. Tumor necrosis factor-α (TNF-α) induces MMPs and may influence anastomosis repair. We assessed the efficacies of the nonselective hydroxamate MMP inhibitor GM6001, the selective hydroxamate MMP inhibitor AG3340 and a TNF-α antagonist with respect to anastomotic breaking strength of left-sided colon anastomoses in male Sprague-Dawley rats. Systemic GM6001 treatment effectively blocked MMP activity and maintained the initial breaking strength day 0 of the anastomoses when administered subcutaneously as daily depositions (100 mg/kg) or continuously (10 mg/kg/day). In contrast, the anastomotic biomechanic strength was lowered by 55% (p < 0.001) in vehicle-treated rats on postoperative day 3. GM6001 treatment increased breaking strength by 88% (p < 0.0005) compared with vehicle-treated rats day 3 and reduced (p = 0.003) the occurrence of spontaneous anastomotic dehiscence. Histologically, the anastomotic wound was narrower (p < 0.05) in the longitudinal direction in GM6001-treated animals whereas GM6001 had no significant effect on inflammatory cell infiltration or epithelialization. AG3340 (10 mg/kg) increased (p < 0.012) breaking strength by 47% compared with vehicle on day 3 but did not significantly prevent the reduction of the initial breaking strength on day 0. Although the increased TNF-α levels in the wound were attenuated, the anastomotic breaking strength was not improved (p = 0.62) by the TNF-α (10 mg/kg) inhibitor given systemically. Pharmacological nonselective MMP inhibition ought to be explored as a prophylactic regimen to reduce anastomotic complications following colorectal resection. The involvement of TNF-α was insignificant in anastomotic wound healing in an experimental model.

Effects of platelet-rich plasma on intestinal wound healing in pigs

Anastomotic dehiscence and leakage remain a major problem in gastrointestinal surgery. Recently, attention has been focused on cellular acceleration of the wound healing process using platelet-rich plasma (PRP) and this study reports the effects of PRP on intestinal wound healing in pigs. Autologous PRP was obtained from 35 pigs that were then subjected to two intestinal anastomosis procedures. Activated PRP was applied at one of the anastomosis sites, while the other site served as control. After 24, 48, 72 and 96 h and then at 7 days, histology was performed and wound breaking strength was measured at 72 h and 7 days. PRP application appeared to increase granulation tissue and fibrosis, but did not influence anastomotic breaking strength.

Anastomotic healing in ileum and colon of alloxan-induced diabetic rats

To investigate if diabetes mellitus may alter breaking strength (BS) and collagen content in ileum and colon anastomoses in rats. Three-hundred Wistar rats were randomly assigned to 5 experimental groups, 60 per group: normal controls surgically manipulated (G1); normal controls submitted to ileum (G2) and colon (G3) anastomotic construction; diabetic rats submitted to ileum (G4) and colon (G5) anastomotic construction. Each group was further divided into 6 subgroups with 10 rats each for sacrifice at 0, 4, 7, 14, 21, and 30 days after surgery. All surgical procedures were performed 3 months after alloxan diabetes induction. BS was measured in all intestinal anastomoses. Fragments of ileum and colon anastomoses were taken for hydroxyproline concentration (HP) and total tissue protein (TP) dosages. Anastomotic BS was significantly decreased (P<0.05) in ileum and colon of G4 and G5 diabetic groups up to 7 and 14 days after surgery, respectively, compared with G2 and G3 normal control groups. Anastomotic HP and TP content did not significantly differ between diabetic and normal control operated groups in ileum or colon at all evaluation times. Experimental diabetes leads to impaired intestinal anastomotic strength during early surgical wound repair, but does not appear to be implicated with collagen synthesis capacity.

Effect of parenteral zinc sulfate on colon anastomosis repair in the rat

To prevent colonic anastomotic dehiscence, pharmaceutical interventions should inhibit degradation of existing submucosal collagen fibers and accelerate the synthesis of new collagen molecules. Zinc has multiple functions in collagen metabolism and was recently found beneficial in colonic anastomosis repair. We have investigated the effect of daily intraperitoneal zinc (2 mg/kg) injections on the development of the biomechanical integrity of left colon anastomoses. Sixty Sprague-Dawley male rats (median 245 g) were allocated to treatment with zinc sulfate in saline (n = 30) or with saline alone (n = 30) starting 1 h before the anastomoses were made. Serum zinc levels and anastomotic breaking strength were determined on postoperative days 3 (n = 30) and 7 (n = 30). The initial breaking strength or suture-binding capacity was determined in additional ten non-treated animals (277 g). The breaking strength of the anastomoses decreased in the two groups combined (n = 30) by 50% (p < 0.001) on day 3 but was regained by postoperative day 7 compared with the initial anastomotic biomechanical strength. Serum zinc levels also increased from day 3 to day 7 in both intervention groups and correlated significantly with breaking strength (r = 0.57, p < 0.001). Although the median serum zinc level was 14% higher (p < 0.01) on day 7 in zinc-treated than in saline-treated animals, the breaking strength did not differ significantly between zinc-treated and saline-treated rats on either day 3 (p = 0.95) or day 7 (p = 0.70). In contrast to previous report in rabbits, we failed to demonstrate the beneficial effects of parenteral zinc supplementation on colon anastomosis repair in a rat model.

The Effect of Azathioprine on Anastomotic Healing: An Experimental Study in Rats

The cytotoxic and immunosuppressive effects of azathioprine, which mitigate the disease activity in inflammatory bowel disease, may compromise the healing of intestinal anastomoses leading to an increased risk of anastomotic leakage. The effect of azathioprine treatment on intestinal healing was tested. In an experimental study, rats were randomly given one oral dose of azathioprine (5 mg or 20 mg/kg body weight per day) or placebo. After 28 days of treatment, a left colonic anastomosis was performed. After three days of healing, the breaking strengths of the anastomoses were tested, along with measurements of azathioprine major metabolite concentrations: 6-thioguanine and 6-methyl-mercaptopurine. There were no significant differences in the anastomotic breaking strength between the three groups. Daily treatment for four weeks with high or low azathioprine doses has no inhibitory effect on colonic healing in rats.

Does the Administration Route of Leucovorin Have Any Influence on the Impairment of Colonic Healing Caused by Intraperitoneal 5-Fluorouracil Treatment?

Intraperitoneal chemotherapy with 5-fluorouracil (5-FU) is a new, promising alternative in adjuvant treatment of advanced colorectal cancer. Leucovorin (LV), a biomodulator of 5-FU, potentiates the antineoplastic effect of 5-FU. The aim of this study was to determine whether the administration routes of LV had any influence on the impairment of colonic healing caused by intraperitoneal 5-FU treatment. 48 male Wistar rats were subjected to left colonic resection and anastomosis, and randomized to 1 of 4 groups: control group (receiving intraperitoneal NaCl, intravenous NaCl); ipFU group (receiving intraperitoneal 5-FU, intravenous NaCl); ipFU+ivLV group (receiving intraperitoneal 5-FU, intravenous LV), and ipFU+LV group (receiving intraperitoneal 5-FU+LV, intravenous NaCl). Treatment was started after surgery and continued for 5 days with daily injections. The animals were sacrificed on the 7th day postoperatively. Anastomotic complications were more common in the ipFU, ipFU+ivLV, and ipFU+LV groups (p < 0.05) compared to the control group. The anastomotic breaking strength was significantly reduced in the ipFU, ipFU+ivLV, ipFU+LV groups (p < 0.05) than in the control group, but it did not differ between the ipFU, ipFU+ivLV, and ipFU+LV groups. The hydroxyproline content of the anastomotic segment was also significantly reduced in the ipFU, ipFU+ivLV and ipFU+LV groups (p < 0.05) compared to the control group. However, there was no difference between the anastomotic hydroxyproline content of the ipFU, ipFU+ivLV, and ipFU+LV groups. In this experiment, colonic healing was impaired after intraperitoneal 5-FU administration as judged by the higher rates of anastomotic complications, reductions in anastomotic breaking strength and hydroxyproline content; but LV administration either intravenously or intraperitoneally did not cause further deterioration in colonic healing.

Inhibition of matrix metalloproteinases enhances breaking strength of colonic anastomoses in an experimental model.

The breaking strength of colonic anastomoses declines after operation to a minimum at days 3-4, with a subsequent risk of anastomotic dehiscence. The mechanism is thought to be collagen degradation by matrix metalloproteinases (MMPs). This study examined the pathogenic role of MMPs on the mechanical strength of colonic anastomoses by giving the synthetic broad-spectrum MMP inhibitor BB-1101 systemically. Forty-eight male Sprague-Dawley rats were treated daily for 7 days with BB-1101 30 mg/kg or vehicle alone (control) starting 2 days before operation. The breaking strength of standardized left-sided colonic anastomoses was measured on postoperative days 1, 3 and 7. Serum BB-1101 levels were increased at 100 nmol/l in BB-1101-treated rats. The anastomotic breaking strength was 48 per cent higher (P = 0.02) in BB-1101-treated animals compared with controls on postoperative day 3. Neither collagen accumulation nor infiltration of neutrophils in the anastomotic area was influenced by BB-1101 treatment. Net deposition of new collagen in subcutaneous sponges was unaffected by the BB-1101. The enhanced breaking strength of colonic anastomoses during the critical early postoperative phase found after administration of a broad-spectrum MMP inhibitor implies that MMPs might increase the risk of anastomotic dehiscence. Presented in part to the third joint meeting of the European Tissue Repair Society and the Wound Healing Society in Bordeaux, France, 24-28 August 1999, and published in abstract form in Wound Repair Regen 1999; 7: A321

Recombinant Growth Hormone's Effects on the Strength and Thickness of Radiation-Injured Ileal Anastomoses: A Rat Model

Background. Small bowel resections following radiotherapy for gynecologic cancers have resulted in significant rates of morbidity and mortality. The objective of this study was to evaluate the effect of rGH on the breaking strength and thickness of radiation-injured ileal anastomoses in an animal model.Materials and methods. Sprague-Dawley rats were treated with 1800 cGy of pelvic irradiation in a single fractionation. Seventeen weeks following pelvic teletherapy an ileo-ileostomy was performed. The rats were randomized to receive 2.0 mg/kg/day of rGH for 7 days or placebo. On the seventh postoperative day a segment of ileum surrounding the anastomosis was resected. The segments were tested for breaking strength or were histologically measured for anastomotic thickness.Results. The ileal anastomotic breaking strength in the rGH group was 181 ± 8.4 g (mean ± standard error). The breaking strength of ileal anastomoses in the placebo group was 133 ± 6.9 g (P < 0.05). The rGH group demonstrated a greater anastomotic thickness (1.65 ± 0.116 mm) than the placebo group (1.17 ± 0.113 mm, P < 0.05). Of placebo rats 14.7% developed anastomotic leaks compared to 0% of rGH-treated animals (P < 0.05).Conclusions. RGH increased the ileal anastomotic breaking strength by 36% in radiated rats. The anastomotic leak rate was reduced from 14.7% in the placebo group to 0% in the rGH group. These findings correlated with a 41% increase in the thickness of the anastomotic connective tissue in the rGH group. Clinical investigation in selected patients is warranted.

Esophagogastric anastomotic wound healing in rats.

Esophagectomy with esophagogastric anastomosis is commonly complicated by anastomotic dehiscence. Although this is a major problem in clinical esophageal surgery, laboratory investigation of esophagogastric anastomotic wound healing has been hampered by the lack of a practical rodent model. Problems with aspiration pneumonia and anastomotic strictures hindered our previous studies in the rat. Other researchers have turned to large animal experiments, or used various upper gastrointestinal pseudoanastomotic techniques in rodents. None of these approaches has proved satisfactory. We developed a technique of side-to-side esophagogastric anastomosis in the rat, and then studied normal esophagogastric anastomotic healing in this model. Anastomoses were performed in 24 rats. Anastomotic breaking strength and hydroxyproline concentration were measured 1 and 2 weeks after surgery. Anastomotic breaking strength was 3.78 +/- 1.18 N at 1 week and 4.83 +/- 0.91 N after 2 weeks (p < 0.03). Anastomotic tissue hydroxyproline concentration was 370.6 +/- 31.2 nmol/mg at 1 week and 462.1 +/- 69.7 nmol/mg after 2 weeks (p < 0.001). Many of the problems encountered in esophagogastric anastomotic studies in the rat have been overcome using this new model.

The Effect of Recombinant Growth Hormone on the Strength of Ileal Anastomoses in a Rat Model

In gynecologic surgery, the ileum is the primary site of bowel injury. Recombinant growth hormone (rGH) has been shown to improve the strength of colonic anastomoses in experimental models. The purpose of this study is to evaluate the effect of rGH on small bowel anastomoses, specifically in the ileum. Twenty large female rats underwent segmental ileal resections and end-to-end ileoileostomies. The rats were randomized to be treated for 7 postoperative days with either rGH (2.0 mg/kg/day) or placebo starting on the day of surgery. On the seventh postoperative day, a segment of ileum surrounding the anastomosis was resected. The anastomoses were tested for breaking strength on a tensiometer and for tissue concentrations of hydroxyproline. The ileal anastomotic breaking strength in the rGH group was 163.5 +/- 6.0 g (mean +/- standard error). In the placebo group, the breaking strength of ileal anastomoses was 125.0 +/- 3.0 g (P < .001). No significant difference was demonstrated with respect to the hydroxyproline concentration between the rGH group (15.2 +/- 2.0 micrograms/mg) and the placebo group (14.6 +/- 1.0 micrograms/mg). In an animal model, a 31% increase in ileal anastomotic breaking strength was induced by rGH administration. With further research this may translate into decreases in the surgical complications that occur in ileal anastomoses. Furthermore, these serve as preliminary data to a study that evaluates the effect of rGH on ileal anastomoses in radiation-injured bowel.