The effect of gender on early colonic anastomotic wound healing

Kjær, Maj‐Brit Nørregaard; Kristjánsdóttir, Hrefna; Andersen, Lars Willy; Heegaard, Anne‐Marie; Ågren, Magnus S.; Jørgensen, Lars N.

doi:10.1007/s00384-018-3089-4

Cited by 18 publications

(18 citation statements)

References 45 publications

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“…TGF- β is closely involved in collagen metabolism during early colonic anastomotic wound healing [ 31 , 32 ]. We have previously shown a correlation between TGF- β 1 and soluble collagen indicative of collagen synthesis in anastomotic healing on day 3 [ 19 ]. TGF- β 1 levels were reduced with ZP1849 treatment on day 5, an observation also reported by Redstone et al [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…The noninjured colon segment was snap-frozen in liquid nitrogen and stored at -80°C until analysed for mRNAs. An end-to-end single-layer anastomosis was made using 8 interrupted, inverted polypropylene monofilament 6/0 sutures (Prolene®) placed 2 mm from the resection margins [ 18 , 19 ]. Saline (37°C) was applied to the abdominal cavity (5 mL) and subcutaneous tissue (2.5 mL).…”

Section: Methodsmentioning

confidence: 99%

“…MPO (EKR284; Nordic BioSite, Täby, Sweden) and TGF- β 1 (ab119558; Abcam, Cambridge, UK) were analysed by rat ELISA kits. Soluble collagens were eluted from the tissue using a buffer (pH 6.0) containing 1 M NaCl for 24 hours at 4°C and determined by the Sircol assay [ 19 ]. MPO, TGF- β 1, and soluble collagen were normalized to total protein determined by the Lowry assay.…”

Section: Methodsmentioning

confidence: 99%

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

Kjær

Russell

Schjerling

et al. 2020

Gastroenterology Research and Practice

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

Kjær

Russell

Schjerling

et al. 2020

Gastroenterology Research and Practice

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“…1 Recent research provides novel evidence that visceral adipose tissue of female mice possesses greater levels of pro-angiogenic factors and vascularity than males in response to a high fat diet, and collagen metabolism is impaired in the colonic anastomosis of male compared with female rats during early wound healing. 21,22 In gonadally intact rodents, it has been suggested that males should be compared to females on specific days of their 4 day estrous cycle to generate reliable data. 23 However, a meta-analysis comparison of male and female rodents, with no regard to the stage of the estrous cycle, established that variability in most traits was equivalent in females and males, and that for most end points, it was unnecessary to stage the estrous cycle.…”

Section: Discussionmentioning

confidence: 99%

“…The NIH has recently recognized this gap in scientific knowledge and now mandates that studies be conducted in both sexes 1 . Recent research provides novel evidence that visceral adipose tissue of female mice possesses greater levels of pro‐angiogenic factors and vascularity than males in response to a high fat diet, and collagen metabolism is impaired in the colonic anastomosis of male compared with female rats during early wound healing 21,22 …”

Section: Discussionmentioning

confidence: 99%

Sex differences in murine myocutaneous flap revascularization

Brandenburg

Clark

Coffman

et al. 2020

Wound Repair Regeneration

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Sex differences in susceptibility to ischemia/reperfusion injury have been documented in humans. Premenopausal women have a lower risk of ischemic heart disease than age-matched men, whereas after menopause, the risk is similar or even higher in women. However, little is known about the effects of sex on myocutaneous ischemia/ reperfusion. To explore sex differences in wound revascularization, we utilized a murine myocutaneous flap model of graded ischemia. A cranial-based, peninsularshaped, myocutaneous flap was surgically created on the dorsum of male and female mice. Physiological, pathological, immunohistochemical, and molecular parameters were analyzed. Flaps created on female mice were re-attached to the recipient site resulting in nearly complete viability at post-operative day 10. In contrast, distal fullthickness myocutaneous necrosis was evident at 10 days post-surgery in male mice. Over the 10 day study interval, laser speckle imaging documented functional revascularization in all flap regions in female mice, but minimal distal flap reperfusion in male mice. Day 10 immunostained histologic sections confirmed significant increases in distal flap vessel count and vascular surface area in female compared to male mice. RT-PCR demonstrated significant differences in growth factor and metabolic gene expression between female and male mice at day 10. In conclusion, in a gradedischemia wound healing model, flap revascularization was more effective in female mice. The recognition and identification of sex-specific wound healing differences may lead to a better understanding of the underlying mechanisms of myocutaneous revascularization and drive novel discovery to improve soft tissue wound healing following tissue transfer for traumatic injury and cancer resection.

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Prediction model of anastomotic leakage after anterior resection for rectal cancer—based on nomogram and multivariate analysis with 1995 patients

Li,

Zhou,

Zhao

et al. 2023

Int J Colorectal Dis

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The effect of gender on early colonic anastomotic wound healing

Abstract: Our findings point towards a less favorable collagen metabolism in colonic anastomoses of male compared with female rats during early wound healing.

Cited by 18 publications

References 45 publications

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

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

Sex differences in murine myocutaneous flap revascularization

Prediction model of anastomotic leakage after anterior resection for rectal cancer—based on nomogram and multivariate analysis with 1995 patients

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