Genomic characterization of the inflammatory response initiated by surgical intervention and the effect of perioperative cyclooxygenase 2 blockade

Coon, Keith D.; Inge, Landon J.; Swetel, Kristen; Felton, Valerie M.; Stafford, Phillip; Bremner, Ross M.

doi:10.1016/j.jtcvs.2010.01.022

Cited by 6 publications

(3 citation statements)

References 22 publications

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“…IL-1β stimulated skin fibroblasts to increase collagen production, whereas colon fibroblasts did not increase production [29]. IL-1β is one of many inflammatory cytokines to be differentially expressed due to COX-2-inhibition [30]. The heterogeneous effect of NSAIDs on different organ systems should be taken into account in future studies when assessing the effect of these substances on wound healing.…”

Section: Discussionmentioning

confidence: 99%

Effect of Postoperative Diclofenac on Anastomotic Healing, Skin Wounds and Subcutaneous Collagen Accumulation: A Randomized, Blinded, Placebo-Controlled, Experimental Study

et al. 2012

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Background: Retrospective studies have drawn attention to possible detrimental effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the anastomotic leakage rate after colorectal resection. In this study, we examined the effects of the NSAID diclofenac on the breaking strength of an experimental colonic anastomosis and a skin incision as well as subcutaneous collagen accumulation. Methods: This was a randomized, blinded, placebo-controlled experimental study in 60 male Wistar rats treated with diclofenac 4 mg/kg/day or placebo. In each rat, a colonic anastomosis was performed and an expanded polytetrafluoroethylene (ePTFE) tube was placed subcutaneously. Incisional and anastomotic wound breaking strength and hydroxyproline content in the ePTFE tubes were measured 7 days after the operation. Results: We found no significant differences in any of the breaking strength measurements, but showed a median 38% reduction in hydroxyproline deposition as a result of diclofenac treatment (p = 0.03). In the placebo group, subcutaneous collagen deposition tended to correlate positively with skin incisional but negatively with anastomotic bio-mechanical strength. Conclusion: Postoperative diclofenac treatment significantly inhibited collagen deposition in subcutaneous granulation tissue. Anastomotic strength and skin wound strength were not significantly affected. The ePTFE model is suitable for assessing the effect of various drugs on collagen formation and thus on wound healing.

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Section: Discussionmentioning

confidence: 99%

Effect of Postoperative Diclofenac on Anastomotic Healing, Skin Wounds and Subcutaneous Collagen Accumulation: A Randomized, Blinded, Placebo-Controlled, Experimental Study

et al. 2012

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“…Nossuli et al (2000) showed that surgical procedure induces significant variations in the expression profiles of inflammatory cytokines, such as IL-6 and TNF-α, in mouse heart. Genomic profiling of the mouse blood cells at 6 h post-surgery displayed a noteworthy change in the gene expression profiles (Coon et al, 2010). More recently, a study by Hoffmann et al (2014) showed that sham-operated and MI animals display a similar monocyte and granulocyte circulation pattern over time, resulting in a background inflammatory response which prohibited the assessment of the MI-induced inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

A Dynamic Transcriptional Analysis Reveals IL-6 Axis as a Prominent Mediator of Surgical Acute Response in Non-ischemic Mouse Heart

et al. 2019

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BackgroundIschemic heart diseases are a major cause of death worldwide. Different animal models, including cardiac surgery, have been developed over time. Unfortunately, the surgery models have been reported to trigger an important inflammatory response that might be an effect modifier, where involved molecular processes have not been fully elucidated yet.ObjectiveWe sought to perform a thorough characterization of the sham effect in the myocardium and identify the interfering inflammatory reaction in order to avoid misinterpretation of the data via systems biology approaches.Methods and ResultsWe combined a comprehensive analytical pipeline of mRNAseq dataset and systems biology analysis to characterize the acute phase response of mouse myocardium at 0 min, 45 min, and 24 h after surgery to better characterize the molecular processes inadvertently induced in sham animals. Our analysis showed that the surgical intervention induced 1209 differentially expressed transcripts (DETs). The clustering of positively co-regulated transcript modules at 45 min fingerprinted the activation of signalization pathways, while positively co-regulated genes at 24 h identified the recruitment of neutrophils and the differentiation of macrophages. In addition, we combined the prediction of transcription factors (TF) regulating DETs with protein-protein interaction networks built from these TFs to predict the molecular network which have induced the DETs. By mean of this retro-analysis of processes upstream gene transcription, we revealed a major role of the Il-6 pathway and further confirmed a significant increase in circulating IL-6 at 45 min after surgery.ConclusionThis study suggests that a strong induction of the IL-6 axis occurs in sham animals over the first 24 h and leads to the induction of inflammation and tissues’ homeostasis processes.

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“…Selective inhibitors of the inducible isoform of cyclooxygenase (COX-2) were developed to provide relief of pain associated with arthritis, surgery, and other conditions, while lowering the incidence of gastrointestinal complications compared to non-selective, non-steroidal anti-inflammatory drugs (nsNSAIDs) 1. However, selective COX-2 inhibitors have been purported to increase the risk of adverse cardiovascular events, such as myocardial infarction, and mortality.…”

Section: Introductionmentioning

confidence: 99%

Effects of selective cyclooxygenase-2 and nonselective cyclooxygenase inhibition on ischemic myocardium

Robich

Chu

Feng

et al. 2010

The Journal of Thoracic and Cardiovascular Surgery

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Objective We sought to explore the effects of non-selective COX and selective COX-2 inhibition on collateral development in a model of chronic myocardial ischemia. We hypothesized that COX-2 inhibitors will negatively effect angiogenic and inflammatory pathways. Methods Yorkshire swine were made chronically ischemic by placing an ameroid constrictor on the left circumflex coronary artery. Swine were divided into three groups and given: no drug (control, n=7), a non-selective COX inhibitor (naproxen 400mg daily, NAP, n=7), or a selective COX-2 inhibitor (celecoxib 200mg daily, CBX, n=7). After 7 weeks, coronary angiography was performed. Myocardial function and microvascular reactivity were assessed. Serum and myocardial tissue were analyzed for prostaglandin levels and markers of inflammation and angiogenesis. Results The CBX group demonstrated significantly increased mean arterial pressure and decreased left ventricular function. Myocardial perfusion in the CBX group was similar to the control, but less than in the NAP group. Coronary microvascular contraction in the collateral dependent territory was increased in the NAP group, but minimally affected in the CBX group. Oxidative stress and apoptosis were increased in the CBX group. Expression of angiogenic markers, VEGF and phospho-eNOS (ser1177), and tissue levels of prostacyclin were decreased in both the CBX and NAP groups. The NAP group had diminished expression of endostatin. Conclusion The effects of selective and non-selective COX inhibition are more complex than previously published, but they do not decrease collateral dependent blood flow to the myocardium in our model of chronic myocardial ischemia.

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Genomic characterization of the inflammatory response initiated by surgical intervention and the effect of perioperative cyclooxygenase 2 blockade

Abstract: Surgical intervention has a dramatic effect on the expression of genes related to the inflammatory response. Perioperative treatment with a cyclooxygenase 2 inhibitor abated many of these changes and might counteract many of the negative effects of the response to surgical intervention.

Cited by 6 publications

References 22 publications

Effect of Postoperative Diclofenac on Anastomotic Healing, Skin Wounds and Subcutaneous Collagen Accumulation: A Randomized, Blinded, Placebo-Controlled, Experimental Study

Effect of Postoperative Diclofenac on Anastomotic Healing, Skin Wounds and Subcutaneous Collagen Accumulation: A Randomized, Blinded, Placebo-Controlled, Experimental Study

A Dynamic Transcriptional Analysis Reveals IL-6 Axis as a Prominent Mediator of Surgical Acute Response in Non-ischemic Mouse Heart

Effects of selective cyclooxygenase-2 and nonselective cyclooxygenase inhibition on ischemic myocardium

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