The effects of tacrolimus on colonic anastomotic healing in rats

Mantzoros, Ioannis; Pramateftakis, Manousos-Georgios; Despoudi, Kalliopi; Zaraboukas, Thomas; Κολιάκος, Γεώργιος; Kanellos, Ioannis; Lazarides, Ch.

doi:10.1007/s00384-011-1337-y

Cited by 14 publications

(18 citation statements)

References 31 publications

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“…Chemotactic agents, cytokines and inflammatory cells are densely found in the anastomosis area on the 2nd day postoperative [21]. An experimental study shows that the inflammatory cell density in the anastomosis area is related to the postoperative day count [22]. No significant difference was observed between inflammatory cell densities of different groups in our study.…”

Section: Discussioncontrasting

confidence: 45%

Comparison of effects of the tacrolimus and cyclosporine A on the colon anastomosis recovery of rats

Uysal

Dokur

2017

Ann Surg Treat Res

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PurposeThis study aims to examine and compare the effects of immunosuppressant cyclosporine A (CsA) and tacrolimus (TAC) on colon anastomosis recovery.MethodsForty rats were randomly divided into 4 groups. The 4 groups were determined as follows: control group; sham group, given %0.09 NaCl; TAC group, given 0.5 mg/kg/day tacrolimus; and CsA group, given 5 mg/kg/day CsA. A 6-cm midabdomen incision was performed on the rats. An incision of all layers on the right colon was performed. Then anastomosis was undertaken. Laparotomy was performed on the seventh day postoperation. The colon bursting pressures were evaluated, histopathological examinations were undertaken, and E-cadherin expression and tissue hydroxyproline levels were evaluated.ResultsStatistically significant differences were observed among bursting pressures of the groups (P < 0.001). The value was significantly low in TAC and CsA groups when compared to control and sham groups (P < 0.05). The tissue hydroxyproline levels were significantly low in TAC group compared to control group (P = 0.03). Fibroblast density and neovascularization were significantly greater in the control group compared to the TAC group (P < 0.05). Levels of collagen had decreased significantly in TAC group compared to other groups (P < 0.05).ConclusionOur study showed that TAC may have a negative effect of colon anastomosis recovery. The lowest anastomosis bursting pressure was detected in TAC group. Also, collagen, hydroxyproline, fibroblast, neovascularization and E-Cadherin levels were comparatively lower in TAC group. CsA did not cause any significant changes to tissue hydroxyproline, collagen, fibroblast, and E-Cadherin levels.

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Section: Discussioncontrasting

confidence: 45%

Comparison of effects of the tacrolimus and cyclosporine A on the colon anastomosis recovery of rats

Uysal

Dokur

2017

Ann Surg Treat Res

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“…Thus, a causative connection between these two substances and DLs appears plausible. Differently, CNIs (both cyclosporine and tacrolimus) have been associated with impaired wound healing but not with anastomotic leakage . However, these studies were conducted as peri‐ and postoperative drug application models only.…”

Section: Discussionmentioning

confidence: 99%

Duodenal leaks after pancreas transplantation with enteric drainage - characteristics and risk factors

et al. 2015

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SummaryPancreas-kidney transplantation with enteric drainage has become a standard treatment in diabetic patients with renal failure. Leaks of the graft duodenum (DL) remain a significant complication after transplantation. We studied incidence and predisposing factors of DLs in both simultaneous pancreas-kidney (SPK) and pancreas after kidney (PAK) transplantation. Between January 2002 and April 2013, 284 pancreas transplantations were performed including 191 SPK (67.3%) and 93 PAK (32.7%). Patient data were analyzed for occurrence of DLs, risk factors, leak etiology, and graft survival. Of 18 DLs (incidence 6.3%), 12 (67%) occurred within the first 100 days after transplantation. Six grafts (33%) were rescued by duodenal segment resection. Risk factors for a DL were PAK transplantation sequence (odds ratio 3.526, P = 0.008) and preoperative immunosuppression (odds ratio 3.328, P = 0.012). In the SPK subgroup, postoperative peak amylase as marker of preservation/reperfusion injury and recipient pretransplantation cardiovascular interventions as marker of atherosclerosis severity were associated with an increased incidence of DLs. CMV-mismatch constellations showed an increased incidence in the SPK subgroup, however without significance probability. Long-term immunosuppression in PAK transplantation is a major risk factor for DLs. Early surgical revision offers the chance of graft rescue.

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“…In all these experimental studies wound repair was analyzed at one time point only. Raptis et al also used a low tacrolimus dose of 0.1 mg/kg/day and reported evidence of enhanced rodent colonic anastomotic healing, measured as bursting pressure at 4 and 8 days postoperatively [16]. …”

Section: Discussionmentioning

confidence: 99%

“…Because inflammatory T cells play a role in wound healing an effect of tacrolimus on wound healing is conceivable. Reported effects of tacrolimus in preclinical studies are contradictory, ranging from stimulation to inhibition of soft tissue repair [11-16]. A common drawback to these studies is the fact that, almost without exception, only one post-operative time point is evaluated, while wound healing is a complex process with different and overlapping phases.…”

Section: Introductionmentioning

confidence: 99%

Tacrolimus Does Not Affect Early Wound Healing in a Rodent Model of Bowel Anastomoses and Abdominal Wall Closure

et al. 2013

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BackgroundUse of immunosuppressant drugs has been associated with complications in wound healing. The calcineurin inhibitor tacrolimus is thought to have a relatively low complication rate, but preclinical research has yielded contradictory data, prompting the current comprehensive studyMethodsThree groups of 33 male Wistar rats received a daily subcutaneous dose of 0,5, 2 or 5 mg/kg tacrolimus. A control group received saline. On day 0 a resection of 1 cm ileum and 1 cm colon was performed, and end-to-end anastomoses were constructed. Ten rats of each group were killed on day 3 and day 5 and the remaining animals on day 7. Both anastomoses and the wound in the abdominal wall were analyzed. Wound strength was the primary outcome parameter.ResultsMean strength of the abdominal wall increased significantly over time in all groups (p<0.0001). Both the breaking strength and the bursting pressure of the ileum and colon anastomoses followed the same pattern. No differences were observed between control and experimental groups. In addition, no consistent differences were found between groups regarding wound hydroxyproline content and the activities of matrix metalloproteinase-2 and -9.ConclusionTacrolimus does not affect early wound healing.

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The effects of tacrolimus on colonic anastomotic healing in rats

Abstract: 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.

Cited by 14 publications

References 31 publications

Comparison of effects of the tacrolimus and cyclosporine A on the colon anastomosis recovery of rats

Comparison of effects of the tacrolimus and cyclosporine A on the colon anastomosis recovery of rats

Duodenal leaks after pancreas transplantation with enteric drainage - characteristics and risk factors

Tacrolimus Does Not Affect Early Wound Healing in a Rodent Model of Bowel Anastomoses and Abdominal Wall Closure

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