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The effect of Ginkgo biloba EGb 761 on intestinal anastomotic healing in rats with ischemia-reperfusion induced in the lower extremities. JOURNAL OF SURGERY AND MEDICINE 2021. [DOI: 10.28982/josam.890700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Nerstrøm M, Krarup PM, Jorgensen LN, Ågren MS. Therapeutic improvement of colonic anastomotic healing under complicated conditions: A systematic review. World J Gastrointest Surg 2016; 8:389-401. [PMID: 27231518 PMCID: PMC4872068 DOI: 10.4240/wjgs.v8.i5.389] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 11/14/2015] [Accepted: 03/09/2016] [Indexed: 02/07/2023] Open
Abstract
AIM: To identify therapeutic agents for the prophylaxis of gastrointestinal anastomotic leakage (AL) under complicated conditions.
METHODS: The PubMed and EMBASE databases were searched for English articles published between January 1975 and September 2014. Studies with the primary purpose of improving anastomotic healing in the colon or rectum under complicated preoperative and/or intraoperative conditions were included. We excluded studies investigating the adverse effects or risk assessment of an active intervention. Furthermore, investigations of biophysical materials, sealants, electrical stimulation and nutrients were excluded. The primary study outcome was biomechanical anastomotic strength or AL. The meta-analysis focused on therapeutic agents that were investigated in one animal model using the same outcome by at least three independent research groups.
RESULTS: The 65 studies included were divided into 7 different complicated animal models: Bowel ischemia, ischemia/reperfusion, bowel obstruction, obstructive jaundice, peritonitis, chemotherapy and radiotherapy. In total, 48 different therapeutic compounds were examined. The majority of investigated agents (65%) were reported as beneficial for anastomotic healing. Twelve of the agents (25%) were tested more than once in the same model, whereas 13 (27%) of the agents were tested in two or more models of complicated healing. Two therapeutic agents met our inclusion criteria for the meta-analysis. Postoperative hyperbaric oxygen therapy significantly increased anastomotic bursting pressure in ischemic colon anastomoses by a mean of 28 mmHg (95%CI: 17 to 39 mmHg, P < 0.00001). Granulocyte macrophage-colony stimulating factor failed to show a significant increase in anastomotic bursting pressure (95%CI: -20 to 21 mmHg, P = 0.97) vs controls in experimental chemotherapeutic models.
CONCLUSION: This systematic review identified potential therapeutic agents, but more studies are needed before concluding that any of these are useful for AL prophylaxis.
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Boersema GSA, Vakalopoulos KA, Kock MCJM, van Ooijen PMA, Havenga K, Kleinrensink GJ, Jeekel J, Lange JF. Is aortoiliac calcification linked to colorectal anastomotic leakage? A case-control study. Int J Surg 2015; 25:123-7. [PMID: 26700199 DOI: 10.1016/j.ijsu.2015.12.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Revised: 11/16/2015] [Accepted: 12/04/2015] [Indexed: 12/17/2022]
Abstract
BACKGROUND Anastomotic leakage in bowel surgery remains a devastating complication. Various risk factors have been uncovered, however, high anastomotic leakage rates are still being reported. This study describes the use of calcification markers of the central abdominal arteries as a prognostic factor for colorectal anastomotic leakage. METHODS This case-control study includes clinical data from three different hospitals. Calcium volume and calcium score of the aortoiliac tract were determined by CT-scan analysis. Cases were all patients with anastomotic leakage after a left-sided anastomosis (n = 30). Three controls were randomly matched for each case. Only patients with a contrast-enhanced pre-operative CT-scan were included. RESULTS The measurements of the calcium score and calcium volume of the different trajectories showed that there was one significant difference with regard to the right external iliac artery. Multiple regression analysis showed a significant different negative odds ratio of the presence of calcium in the right external iliac artery. CONCLUSION This study demonstrates that calcium volume and calcium score of the aortoiliac trajectory does not correlate with the risk of colorectal anastomotic leakage after a left-sided anastomosis.
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Affiliation(s)
- G S A Boersema
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.
| | - K A Vakalopoulos
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - M C J M Kock
- Department of Radiology, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | - P M A van Ooijen
- Department of Radiology, Medical University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - K Havenga
- Department of Surgery, Medical University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - G J Kleinrensink
- Department of Neuroscience-Anatomy, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - J Jeekel
- Department of Neuroscience-Anatomy, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - J F Lange
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
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Kornmann VNN, van Werkum MH, Bollen TL, van Ramshorst B, Boerma D. Compromised visceral circulation does not affect the outcome of colorectal surgery. Surg Today 2013; 44:1220-6. [PMID: 24081725 DOI: 10.1007/s00595-013-0730-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2013] [Accepted: 06/04/2013] [Indexed: 12/18/2022]
Abstract
PURPOSE Anastomotic leakage is a serious complication after colorectal surgery, and many risk factors for this problem have so far been identified. The aim of this study was to assess the association between visceral arterial occlusive disease and anastomotic leakage. METHODS The preoperative abdominal computed tomography scans from all consecutive patients who underwent colorectal surgery with anastomosis in 2010 were retrospectively analyzed. RESULTS A total of 242 patients were included, with a median age of 65 years (interquartile range 55-74). Anastomotic leakage occurred in 14 % of cases (n = 34). The mortality rate was 3 % (n = 8). There was no association between atherosclerosis of the visceral or iliac arteries and anastomotic leakage. There was also no association between right-sided or left-sided resections and total occlusion of the superior or inferior mesenteric artery, respectively. CONCLUSION Asymptomatic visceral artery occlusive disease is not a risk factor for anastomotic leakage after colorectal surgery, and additional radiological imaging or percutaneous transluminal angioplasty for occluded visceral vessels is not indicated prior to colorectal surgery.
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Affiliation(s)
- Verena N N Kornmann
- Department of Surgery and Vascular Surgery, St. Antonius Hospital, 3435 CM, Nieuwegein, The Netherlands,
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Zambas NA, Karkos CD, Kambaroudis AG, Karamanos DG, Spyridis CT, Gerassimidis TS. Protective Effect of Antithrombin III Against Lung and Myocardial Injury in Lower-Limb Ischemia–Reperfusion Syndrome. Ann Vasc Surg 2012; 26:566-70. [DOI: 10.1016/j.avsg.2012.01.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2011] [Revised: 01/08/2012] [Accepted: 01/14/2012] [Indexed: 11/25/2022]
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Miranda EF, Greca FH, Noronha L, Kotze LR, Rubin MR. The influence of methylene blue on the healing of intestinal anastomoses subjected to ischemia and reperfusion in rats. Acta Cir Bras 2010; 25:63-70. [DOI: 10.1590/s0102-86502010000100015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2009] [Accepted: 11/19/2009] [Indexed: 11/22/2022] Open
Abstract
PURPOSE: To investigate the influence of methylene blue, on the healing of intestinal anastomoses subjected to ischemia and reperfusion in rats. METHODS: Forty-five rats divided into the following three groups were used: control (G1); ischemia without methylene blue (G2); and ischemia with methylene blue (G3). A laparotomy was performed and the cranial mesenteric artery isolated. Whereas the cranial artery was temporarily occluded for 45 minutes in groups G2 and G3, prior to enterotomy and intestinal anastomosis, in group G1 the enterotomy and intestinal anastomosis were performed without prior lesion. Afterwards, 2mL of 0.5% methylene blue were instilled in the peritoneal cavities of the animals in group G3, and 2mL of isotonic saline solution in the peritoneal cavities of the animals in group G2. After the reperfusion, an enterectomy and intestinal anastomosis were performed. After the animals had been sacrificed on the seventh day after the operation, the abdominal cavity was examined by resection of a segment of the intestine containing the anastomosis in order to measure its strength and for histopathological examination. RESULTS: Free fluid or abscesses in the peritoneal cavity were rare. When inflammation was analyzed, the group subjected to ischemia without methylene blue had a higher score for mononuclear cells (p=0.021) and granulation tissue (p=0.044). No significant difference was observed in the density of type I or type III collagens. CONCLUSION: The methylene blue did not show beneficial effect on the healing of intestinal anastomoses subjected to ischemia and reperfusion in rats.
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Unal B, Karabeyoglu M, Huner T, Canbay E, Eroglu A, Yildirim O, Dolapci M, Bilgihan A, Cengiz O. Ethyl pyruvate protects colonic anastomosis from ischemia-reperfusion injury. Surg Innov 2008; 16:21-5. [PMID: 19064591 DOI: 10.1177/1553350608328584] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Ethyl pyruvate is a simple derivative in Ca(+2)- and K(+)-containing balanced salt solution of pyruvate to avoid the problems associated with the instability of pyruvate in solution. It has been shown to ameliorate the effects of ischemia-reperfusion (I/R) injury in many organs. It has also been shown that I/R injury delays the healing of colonic anastomosis. In this study, the effect of ethyl pyruvate on the healing of colon anastomosis and anastomotic strength after I/R injury was investigated. Anastomosis of the colon was performed in 32 adult male Wistar albino rats divided into 4 groups of 8 individuals: (1) sham-operated control group (group 1); (2) 30 minutes of intestinal I/R by superior mesenteric artery occlusion (group 2); (3) I/R+ ethyl pyruvate (group 3), ethyl pyruvate was administered as a 50-mg/kg/d single dose; and (4) I/R+ ethyl pyruvate (group 4), ethyl pyruvate administration was repeatedly (every 6 hours) at the same dose (50 mg/kg). On the fifth postoperative day, animals were killed. Perianastomotic tissue hydroxyproline contents and anastomotic bursting pressures were measured in all groups. When the anastomotic bursting pressures and tissue hydroxyproline contents were compared, it was found that they were decreased in group 2 when compared with groups 1, 3, and 4 (P < .05). Both anastomotic bursting pressure (P = .005) and hydroxyproline content (P < .001) levels were found to be significantly increased with ethyl pyruvate administration when compared with group 2. When ethyl pyruvate administration doses were compared, a significant difference was not observed (P > .05). Ethyl pyruvate significantly prevents the delaying effect of I/R injury on anastomotic strength and healing independent from doses of administration.
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Affiliation(s)
- B Unal
- Department of Surgery, Faculty of Medicine, Inonu University, Malatya, Turkey
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Teke Z, Sacar M, Yenisey C, Atalay AO, Bicakci T, Erdem E. 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. Am J Surg 2008; 196:774-87. [PMID: 18466864 DOI: 10.1016/j.amjsurg.2007.09.039] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2007] [Revised: 09/13/2007] [Accepted: 09/13/2007] [Indexed: 12/22/2022]
Abstract
BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSION 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.
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Affiliation(s)
- Zafer Teke
- Department of General Surgery, Pamukkale University, School of Medicine, 20070, Kinikli, Denizli, Turkey.
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Teke Z, Aytekin FO, Kabay B, Yenisey C, Aydin C, Tekin K, Sacar M, Ozden A. Pyrrolidine dithiocarbamate prevents deleterious effects of remote ischemia/reperfusion injury on healing of colonic anastomoses in rats. World J Surg 2007; 31:1835-1842. [PMID: 17566823 DOI: 10.1007/s00268-007-9106-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND Pyrrolidine dithiocarbamate (PDTC) is a low-molecular-weight thiol antioxidant and potent inhibitor of nuclear factor-kappaB (NF-kappaB) 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.
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Affiliation(s)
- Zafer Teke
- Department of General Surgery, Pamukkale University, Faculty of Medicine, 20070, Kinikli, Denizli, Turkey.
| | - Faruk Onder Aytekin
- Department of General Surgery, Pamukkale University, Faculty of Medicine, 20070, Kinikli, Denizli, Turkey
| | - Burhan Kabay
- Department of General Surgery, Pamukkale University, Faculty of Medicine, 20070, Kinikli, Denizli, Turkey
| | - Cigdem Yenisey
- Department of Biochemistry, Adnan Menderes University, Faculty of Medicine, 09100, Aydin, Turkey
| | - Cagatay Aydin
- Department of General Surgery, Pamukkale University, Faculty of Medicine, 20070, Kinikli, Denizli, Turkey
| | - Koray Tekin
- Department of General Surgery, Pamukkale University, Faculty of Medicine, 20070, Kinikli, Denizli, Turkey
| | - Mustafa Sacar
- Department of Cardiovascular Surgery, Pamukkale University, Faculty of Medicine, 20070, Kinikli, Denizli, Turkey
| | - Akin Ozden
- Department of General Surgery, Pamukkale University, Faculty of Medicine, 20070, Kinikli, Denizli, Turkey
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Posma LAE, Bleichrodt RP, van Goor H, Hendriks T. A prolonged interval between deep intestinal ischemia and anastomotic construction does not impair wound strength in the rat. Int J Colorectal Dis 2007; 22:1485-91. [PMID: 17605022 DOI: 10.1007/s00384-007-0333-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/22/2007] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Transient intestinal ischemia can reduce anastomotic strength, which poses an increased risk of complications. The objective of this study is to establish if a prolonged interval between profound ischemia and construction of an anastomosis affects anastomotic strength. METHODS Male Wistar rats were used: in experimental groups, profound mesenteric ischemia was induced by clamping both superior mesenteric artery and more distal arteries in the ileal mesentery. Resection and anastomosis in ileum and colon were performed immediately (IR0) or 24 h after releasing the clamps (IR24). In controls (C0 and C24), arteries were not clamped. After 5 days, anastomotic bursting pressure (BP), breaking strength (BS), and hydroxyproline were measured, and histological analysis was performed. RESULTS Mortality and anastomotic dehiscence rates were significantly higher in IR0 compared to C0. In ileum, the BS was 34% lower (p<0.05) in IR0 compared to C0, while there were no significant differences in BS or BP between the IR24 and C24 groups. In colon anastomoses, although no differences in BS and BP were found, bursting site was at the anastomosis in 82% in group IR0 vs 30% in group C0, reflecting reduced anastomotic strength in the former. Again, after 24 h, there were no differences between IR and C group. Hydroxyproline and histology were not different between groups. CONCLUSIONS Extending the interval between transient deep intestinal ischemia and construction of an anastomosis does not impair wound strength.
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Affiliation(s)
- Lisanne A E Posma
- Department of Surgery, Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
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Posma LAE, Bleichrodt RP, van Goor H, Hendriks T. Transient profound mesenteric ischemia strongly affects the strength of intestinal anastomoses in the rat. Dis Colon Rectum 2007; 50:1070-9. [PMID: 17205202 DOI: 10.1007/s10350-006-0822-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE Experimental data suggest that transient preoperative ischemia and reperfusion may compromise anastomotic strength. However, data on this subject are equivocal, in particular as to the onset and duration of this effect. This study was designed to comprehensively characterize the effects of profound transient intestinal ischemia on anastomotic healing during the first postoperative week. METHODS Ischemia was induced in rats by clamping both the superior mesenteric artery and ileal branches for 30 minutes. Immediately after declamping, anastomoses were constructed in both terminal ileum and descending colon. After three, five, or seven days, both bursting pressure and breaking strength were measured. Anastomotic collagen content, gelatinase activity, and histology were analyzed. RESULTS Anastomotic leakage rate was 13 percent in ischemia-reperfusion group and 0 percent (P=0.02) in controls. The breaking strength in ileum remained significantly (P<0.05) lower in the ischemic groups than in the control groups at all time points. Bursting pressure in the ileum was not significantly different between ischemic and control groups at either of the time points measured. However, at Day 7 the bursting site was significantly more frequent within the suture line in the ischemic groups. In the colon, at Day 3 the bursting pressure was 35 percent lower in the ischemic group than in the control group (P<0.05). Anastomotic collagen content and gelatinase activity were similar in ischemic and control groups. CONCLUSIONS Transient profound splanchnic ischemia compromises anastomotic strength throughout the entire first postoperative week. This effect does not seem to be caused by impaired accumulation of wound collagen.
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Affiliation(s)
- Lisanne A E Posma
- Department of Surgery, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
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Feistritzer C, Wiedermann CJ. Effects of anticoagulant strategies on activation of inflammation and coagulation. Expert Opin Biol Ther 2007; 7:855-70. [PMID: 17555371 DOI: 10.1517/14712598.7.6.855] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Acute inflammatory events, such as those that occur in sepsis, lead to dysregulation of the coagulation cascade. The hemostatic imbalance in sepsis, characterized by the excessive activation of procoagulant pathways and the impairment of anticoagulant activity, leads to disseminated intravascular coagulation and results in microvascular thrombosis, tissue hypoperfusion and, ultimately, multiple organ failure and death. Furthermore, natural anti-inflammatory mechanisms of the endogenous anticoagulants are diminished by the impaired coagulation. Supportive strategies aiming at inhibiting activation of coagulation and inflammation by treatment with exogenous anticoagulants have been found to be beneficial in experimental and initial clinical studies. This review summarizes the available experimental and clinical data regarding the interaction between coagulation and inflammation, focusing on the two anticoagulants which are in clinical use, antithrombin and activated protein C. Identification of the different biological mechanisms of the two endogenous anticoagulants might help to determine target patient populations as well as to develop new anticoagulant analogs that differ in there respective effects in coagulation and inflammation.
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Affiliation(s)
- Clemens Feistritzer
- Medical University of Innsbruck, Department of Internal Medicine, Innsbruck (Tyrol), Austria
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Kabay B, Teke Z, Aytekin FO, Yenisey C, Bir F, Sacar M, Erdem E, Ozden A. Pyrrolidine Dithiocarbamate Reduces Lung Injury Caused by Mesenteric Ischemia/Reperfusion in a Rat Model. World J Surg 2007; 31:1707-15. [PMID: 17551782 DOI: 10.1007/s00268-007-9112-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
BACKGROUND Pyrrolidine dithiocarbamate (PDTC) is a low-molecular thiol antioxidant and potent inhibitor of nuclear factor-kappaB (NF-kappaB) activation. It has been shown to attenuate local harmful effects of ischemia/reperfusion (I/R) injury in many organs. In this study, we aimed to study the effect of PDTC on lung reperfusion injury induced by superior mesenteric occlusion. METHODS Male Wistar-albino rats randomized into three groups: (1) sham-operated control group (n = 12), laparotomy without I/R injury; (2) intestinal ischemia/reperfusion (I/R) group (n = 12), 60 min of ischemia by superior mesenteric occlusion followed by 2 h of reperfusion; and (3) I/R+PDTC-treated group (n = 12), 100 mg/kg injection of PDTC intravenously, 30 min after the commencement of reperfusion. Evans blue dye was injected to half of rats in all groups before the induction of I/R. We assessed the degree of pulmonary tissue injury biochemically by measuring malondialdehyde (MDA), glutathione (GSH), and nitric oxide (NO) levels, and histopathologically by establishing pulmonary neutrophil sequestration and acute lung injury scoring. Pulmonary edema was evaluated by Evans blue dye extravasation, as well as lung tissue wet/dry weight ratios. RESULTS Pyrrolidine dithiocarbamate treatment significantly reduced the MDA and NO levels, and increased the GSH levels in the lung parenchyma, biochemically (p < 0.05), and atteneuated the pulmonary parenchymal damage, histopathologically (p < 0.05). However, pulmonary neutrophil sequestration was not affected by postischemic treatment with PDTC (p > 0.05). Pyrrolidine dithiocarbamate administration also significantly alleviated the formation of pulmonary edema, as evidenced by the decreased Evans blue dye extravasation and organ wet/dry weight ratios (p < 0.05). CONCLUSIONS This study showed that postischemic treatment with PDTC significantly attenuated the lung reperfusion injury. Further clinical studies are needed for better understanding of the specific mechanisms of PDTC protection against I/R-related organ injury and to clarify whether PDTC may be a useful therapeutic agent during particular operations where remote organ I/R injury occurs.
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Affiliation(s)
- Burhan Kabay
- Department of General Surgery, Pamukkale University, School of Medicine, 20070, Denizli, Turkey
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Aydin C, Teke Z, Aytekin F, Yenisey C, Kabay B, Simsek NG, Tekin K. Tempol prevents harmful effects of remote ischemia reperfusion injury on healing of experimental colonic anastomoses. Int J Colorectal Dis 2007; 22:325-31. [PMID: 16718449 DOI: 10.1007/s00384-006-0149-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/13/2006] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) is a water-soluble analogue of the spin label TEMPO. As an antioxidative agent, it is a member of nitroxides, which detoxifies superoxide and possibly other toxic radicals in vivo. In this study, we aimed to investigate whether tempol prevents harmful systemic effects of superior mesenteric ischemia-reperfusion on left colonic anastomosis in rats. MATERIALS AND METHODS Anastomosis of the left colon was performed in 30 rats that were divided into three groups each having ten animals: sham-operated control (group I), 60 min of intestinal ischemia-reperfusion by superior mesenteric artery occlusion (group II), and tempol-treated group (30 mg/kg before and after the ischemia-reperfusion (group III). On postoperative day 5, all animals were killed and anastomotic bursting pressures were measured in vivo. Tissue samples were obtained for further investigation of anastomotic hydroxyproline content, perianastomotic malondialdehyde, and glutathione levels. RESULTS There was a statistically significant increase in the quantity of myeloperoxidase activity and malondialdehyde levels in group II, along with a decrease in glutathione levels, anastomotic hydroxyproline content, and bursting pressure values when compared to controls. However, all of the investigated parameters were normalized in tempol-treated animals (group III). CONCLUSION We conclude that tempol significantly prevents harmful systemic effects of reperfusion injury on colonic anastomoses in a rat model of superior mesenteric artery occlusion.
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Affiliation(s)
- Cagatay Aydin
- Faculty of Medicine, Genel Cerrahi Anabilim Dali, Kinikli, Pamukkale University, Denizli, 20070, Turkey.
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Erman T, Yildiz MS, Göçer AI, Zorludemir S, Demirhindi H, Tuna M. Effects of antithrombin III on myeloperoxidase activity, superoxide dismutase activity, and malondialdehyde levels and histopathological findings after spinal cord injury in the rat. Neurosurgery 2006; 56:828-35. [PMID: 15792522 DOI: 10.1227/01.neu.0000157004.19427.35] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2004] [Accepted: 11/01/2004] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVE Among the many possible mechanisms of the secondary spinal cord injury (SCI), microcirculatory disturbances as a result of activated leukocyte-induced endothelial cell injury is important because it is potentially treatable and reversible. Currently, clinically available pharmacological agents for treatment of acute SCI do not inhibit neutrophil activation. The effect of antithrombin III (AT-III) on neutrophil activation was studied in rats with SCI produced with an aneurysm clip on the T2-T7 segments. METHODS Forty rats were randomly allocated to four groups. Group I (10 rats) was killed to provide normal spinal cord tissue for testing. Group II (10 rats) underwent a six-segment laminectomy for the effects of total laminectomy to be determined. In Group III, 10 rats underwent a six-segment laminectomy and SCI was produced by extradural compression of the exposed cord. The same procedures were performed in 10 rats in Group IV, but they also received one (250 IU/kg) intraperitoneal injection of AT-III immediately after the injury and a second dose 24 hours later. The animals from Groups II through IV were killed 48 hours after the trauma. The effect of AT-III on the myeloperoxidase activity, superoxide dismutase activity, and malondialdehyde levels and histopathological findings were studied. RESULTS Myeloperoxidase activity, superoxide dismutase activity, and malondialdehyde levels were significantly lower and there was less histopathological damage in the AT-III treatment group than in the trauma group. CONCLUSION The results demonstrate that AT-III treatment may reduce secondary structural changes in damaged rat spinal cord tissue by inhibiting leukocyte activation.
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Affiliation(s)
- Tahsin Erman
- Department of Neurosurgery, Cukurova University School of Medicine, Adana, Turkey.
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Posma LAE, Bleichrodt RP, van Goor H, Hendriks T. Ischemia and prolonged reperfusion before anastomotic construction do not reduce wound strength in the rat intestine. Surgery 2006; 139:671-7. [PMID: 16701101 DOI: 10.1016/j.surg.2005.10.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2005] [Revised: 10/13/2005] [Accepted: 10/22/2005] [Indexed: 10/24/2022]
Abstract
BACKGROUND Under certain conditions, transient intestinal ischemia can reduce anastomotic strength. Preliminary findings suggest that prolonged reperfusion time, before anastomotic construction, results in reduced wound strength. The purpose of this study is to determine if wound strength indeed decreases with increasing duration of the interval between an ischemic period and construction of an anastomosis. METHODS In male Wistar rats, ischemia was induced by crossclamping the superior mesenteric artery (SMA) for 40 minutes. In control groups, the SMA was exposed but not clamped. Resection and anastomosis in both ileum and colon were performed immediately after release of the clamp or after 90 minutes or 24 hours. Both the anastomotic bursting pressure and breaking strength were measured after 3 or 5 days, together with hydroxyproline levels. RESULTS Neither bursting pressure nor breaking strength, either in ileum or in colon, changed significantly when the time between the end of ischemia and anastomotic construction increased. Similar values were obtained in all experimental and corresponding control groups. In the group in which anastomoses were constructed after 24-hour reperfusion, mechanical strength increased significantly from day 3 to day 5 and at the same rate as in the control group. No differences in anastomotic hydroxyproline levels were found between experimental and control groups analyzed at day 5. CONCLUSIONS A prolonged interval between intestinal ischemia and anastomotic construction does not affect development of early wound strength. Therefore, delayed anastomosis after transient ischemia is not likely to increase the risk of anastomotic complications.
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Affiliation(s)
- Lisanne A E Posma
- Department of Surgery, Radboud University Nijmegen Medical Center, The Netherlands.
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Aydin C, Aytekin FO, Tekin K, Kabay B, Yenisey C, Kocbil G, Ozden A. Effect of Temporary Abdominal Closure on Colonic Anastomosis and Postoperative Adhesions in Experimental Secondary Peritonitis. World J Surg 2006; 30:612-9. [PMID: 16479336 DOI: 10.1007/s00268-005-0511-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
BACKGROUND The effect of relaparotomies and temporary abdominal closure on colonic anastomoses and postoperative adhesions is under debate. METHODS In the experiments reported here, colonic anastomosis was constructed 24 hours after cecal ligation and puncture in rats that were divided into three groups of eight animals each. The abdomen was closed primarily in groups I and II, and a Bogota bag was used for abdominal closure in group III. At 24 hours following anastomosis, relaparotomy was performed only in group II and III rats, and the abdomen was closed directly in group II; after removal of the Bogota bag in group III animals, the abdomen was closed directly. On the fifth day of anastomotic construction, bursting pressures and tissue hydroxyproline content of the anastomoses, along with peritoneal adhesions, were assessed and compared. RESULTS Mean anastomotic bursting pressures and hydroxyproline contents did not differ among the groups. Median adhesion scores were significantly higher in group III than the other two groups. CONCLUSIONS Relaparotomy and the type of temporary closure have no negative effect on anastomotic healing in rats with peritonitis. Temporary abdominal closure with a Bogota bag caused a significantly high rate of adhesions.
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Affiliation(s)
- Cagatay Aydin
- Department of Surgery, Pamukkale University, School of Medicine, Kinikli, Denizli, 20070 Turkey.
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Aytekin FO, Tekin K, Kabay B, Erdem E, Guney Y, Firat P, Sungurtekin U, Kaya SO, Ozden A. Antithrombin III attenuates pulmonary tissue injury caused by mesenteric ischemia-reperfusion. Am J Surg 2005; 189:161-6. [PMID: 15720983 DOI: 10.1016/j.amjsurg.2004.11.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2004] [Revised: 04/30/2004] [Indexed: 12/21/2022]
Abstract
BACKGROUND Mesenteric ischemia-reperfusion (I/R) is a well-known event causing both local and remote organ injuries, including the lungs. Recently, several studies indicated that activated leukocyte-endothelial cell interactions play an important role in the mechanisms of these injuries. As a natural inhibitor of serine proteases, antithrombin was shown previously to attenuate the tissue damage after local I/R in several organ systems. Here, we examined the effects of antithrombin on pulmonary injury after mesenteric I/R. METHODS Wistar albino rats underwent median laparotomy and were randomized into 3 groups: (1) sham-operated control (n = 12), (2) 60 minutes of mesenteric ischemia and 3 hours of reperfusion (n = 12), and (3) antithrombin-pretreated (250 U/kg) group before the I/R (n = 12). At the end of reperfusion, animals were killed and neutrophil sequestration, myeloperoxidase (MPO) activity, and Evans blue dye extravasation in the lung parenchyma were assessed and compared. RESULTS There was a statistically significant increase in the quantity of Evans blue dye concentration, leukocyte sequestration, and MPO activity in the I/R group when compared with the control group. The pretreatment of animals with antithrombin significantly decreased the pulmonary injury characterized by increased Evans blue dye extravasation, leukocyte sequestration, and MPO activity. CONCLUSION The data of the present study suggest that mesenteric ischemia and reperfusion induces pulmonary injury characterized by activated neutrophil sequestration and increased microvascular leakage in the lungs. A significant attenuation of intestinal I/R-related lung injury with the use of antithrombin concentrate warrants further studies to elucidate the potential role of this natural serine protease inhibitor in clinical settings.
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Affiliation(s)
- Faruk O Aytekin
- Department of General Surgery, Pamukkale University, Medical School, Denizli, Turkey.
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