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Activated protein C prevents deleterious effects of remote reperfusion injury caused by intestinal ischemia on wound healing in the left colonic anastomoses: an experimental study in the murine model

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Název: Activated protein C prevents deleterious effects of remote reperfusion injury caused by intestinal ischemia on wound healing in the left colonic anastomoses: an experimental study in the murine model
Autoři: Teke, Zafer, Sacar, M., Yenisey, C., Atalay, A.O., Bicakci, T., Erdem, Ergün
Zdroj: The American Journal of Surgery. 196:774-787
Informace o vydavateli: Elsevier BV, 2008.
Rok vydání: 2008
Témata: Male, wound healing, Bursting pressures, pressure, Mice, Random Allocation, 0302 clinical medicine, Ischemia, Surgical, Malondialdehyde, cytokine, hydroxyproline, postoperative complication, rat, Anastomosis, Surgical, article, superior mesenteric artery, drotrecogin, reperfusion injury, Glutathione, colon anastomosis, Mesenteric Arteries, 3. Good health, Intestines, Glutathione Reductase, priority journal, Reperfusion Injury, D dimer, Xanthine Oxidase, Anastomosis, animal experiment, Ischemia/reperfusion, Wound healing, Colonic anastomosis, intestine ischemia, animal tissue, 03 medical and health sciences, male, nitrate, Animals, controlled study, Nitrites, Peroxidase, Wound Healing, Analysis of Variance, nonhuman, Chi-Square Distribution, Nitrates, Interleukin-6, Tumor Necrosis Factor-alpha, animal model, activated protein C, Glutathione/metabolism, Glutathione Reductase/metabolism, Interleukin-6/metabolism, Intestines/*blood supply/*surgery, Ischemia/complications/*prevention & control, Malondialdehyde/metabolism, Mesenteric Arteries/surgery, Nitrates/metabolism, Nitrites/metabolism, Peroxidase/metabolism, Protein C/*pharmacology, Reperfusion Injury/etiology/*prevention & control, enzyme, Activated protein C, Protein C
Popis: Activated protein C (APC) is a serine protease with anticoagulant and antiinflammatory activities. The delaying effects of remote reperfusion injury on the wound-healing process in colonic anastomoses have been previously shown. In this study, we aimed to investigate whether APC protects against deleterious systemic effects of intestinal ischemia/reperfusion (I/R) injury on colonic anastomotic wound healing process.Male Wistar-albino rats were randomly allocated into 4 groups, and a left colonic anastomosis was performed in all animals: (1) sham-operated group, simultaneously with left colonic anastomosis, the superior mesenteric artery and collateral branches were divided from the celiac axis, and the inferior mesenteric artery were isolated but not occluded (group 1, n = 12), (2) sham + APC group, identical to group 1 except for APC treatment (100 microg/kg, intravenously, 15 minutes before construction of the colonic anastomosis), (group 2, n = 12), (3) intestinal I/R group, 60 minutes of superior mesenteric ischemia followed by reperfusion (group 3, n = 12), and (4) APC-treated group, (100 microg/kg, intravenously, 15 minutes before reperfusion) (group 4, n = 12). All animals were sacrificed, and colonic anastomotic bursting pressures were measured in vivo on day 7. Tissue samples were obtained for analysis of hydroxyproline contents, nitrate/nitrite levels, and activities of oxidative and antioxidative enzymes. The plasma levels of proinflammatory cytokines and D-dimer were also measured.Intestinal I/R led to significant decreases in colonic anastomotic bursting pressures, tissue hydroxyproline contents, and activities of antioxidative enzymes, along with increases in tissue nitrate/nitrite levels, activities of oxidative enzymes, and plasma levels of proinflammatory cytokines and D-dimer (P < .05). However, APC treatment led to significant increases in colonic anastomotic bursting pressures, tissue hydroxyproline contents, and activities of antioxidative enzymes, along with decreases in tissue nitrate/nitrite levels, activities of oxidative enzymes, and plasma levels of proinflammatory cytokines and D-dimer (P < .05).This study clearly showed that APC treatment prevented the delaying effects of remote I/R injury on colonic anastomotic wound healing process. Further clinical studies are required to determine whether APC has a useful role in the enhancement of colonic anastomotic wound healing after particular operations in which I/R injury occurs.
Druh dokumentu: Article
Jazyk: English
ISSN: 0002-9610
DOI: 10.1016/j.amjsurg.2007.09.039
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/18466864
https://www.sciencedirect.com/science/article/pii/S0002961008002043
http://www.ncbi.nlm.nih.gov/pubmed/18466864
http://acikerisim.pau.edu.tr:8080/xmlui/handle/11499/7022
Rights: Elsevier TDM
Přístupové číslo: edsair.doi.dedup.....eb12c4c95958b1fa9e82cc0cafb7b6dd
Databáze: OpenAIRE
Popis
Abstrakt:Activated protein C (APC) is a serine protease with anticoagulant and antiinflammatory activities. The delaying effects of remote reperfusion injury on the wound-healing process in colonic anastomoses have been previously shown. In this study, we aimed to investigate whether APC protects against deleterious systemic effects of intestinal ischemia/reperfusion (I/R) injury on colonic anastomotic wound healing process.Male Wistar-albino rats were randomly allocated into 4 groups, and a left colonic anastomosis was performed in all animals: (1) sham-operated group, simultaneously with left colonic anastomosis, the superior mesenteric artery and collateral branches were divided from the celiac axis, and the inferior mesenteric artery were isolated but not occluded (group 1, n = 12), (2) sham + APC group, identical to group 1 except for APC treatment (100 microg/kg, intravenously, 15 minutes before construction of the colonic anastomosis), (group 2, n = 12), (3) intestinal I/R group, 60 minutes of superior mesenteric ischemia followed by reperfusion (group 3, n = 12), and (4) APC-treated group, (100 microg/kg, intravenously, 15 minutes before reperfusion) (group 4, n = 12). All animals were sacrificed, and colonic anastomotic bursting pressures were measured in vivo on day 7. Tissue samples were obtained for analysis of hydroxyproline contents, nitrate/nitrite levels, and activities of oxidative and antioxidative enzymes. The plasma levels of proinflammatory cytokines and D-dimer were also measured.Intestinal I/R led to significant decreases in colonic anastomotic bursting pressures, tissue hydroxyproline contents, and activities of antioxidative enzymes, along with increases in tissue nitrate/nitrite levels, activities of oxidative enzymes, and plasma levels of proinflammatory cytokines and D-dimer (P < .05). However, APC treatment led to significant increases in colonic anastomotic bursting pressures, tissue hydroxyproline contents, and activities of antioxidative enzymes, along with decreases in tissue nitrate/nitrite levels, activities of oxidative enzymes, and plasma levels of proinflammatory cytokines and D-dimer (P < .05).This study clearly showed that APC treatment prevented the delaying effects of remote I/R injury on colonic anastomotic wound healing process. Further clinical studies are required to determine whether APC has a useful role in the enhancement of colonic anastomotic wound healing after particular operations in which I/R injury occurs.
ISSN:00029610
DOI:10.1016/j.amjsurg.2007.09.039