RNA Interference Targeting Hypoxia Inducible Factor 1α Reduces Post-Operative Adhesions in Rats

Segura, Tatiana; Schmökel, Hugo; Hubbell, Jeffrey A.

doi:10.1016/j.jss.2006.07.045

Cited by 38 publications

(21 citation statements)

References 40 publications

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“…Our study demonstrates that the frequently used HKG, that is, GAPDH, is not suitable for normalization of adhesion tissue and therefore could account for the variation of results obtained by these studies (21)(22)(23). Our study shows that GAPDH expression is unstable across tissue types, a finding that is consistent with other studies (24).…”

Section: Discussionsupporting

confidence: 86%

Variation in stability of housekeeping genes in healthy and adhesion-related mesothelium

Sadek

Cagampang

Bruce

et al. 2012

Fertility and Sterility

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Section: Discussionsupporting

confidence: 86%

Variation in stability of housekeeping genes in healthy and adhesion-related mesothelium

Sadek

Cagampang

Bruce

et al. 2012

Fertility and Sterility

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“…36 Although this finding is consistent with others, 37,38 evidence showing that downregulating the HIF-1 α gene reduced adhesion formation is far more substantive evidence that hypoxia plays and important role in early adhesiogenic events. 39 We have also shown in our rat model that there is a significant increase in the expression pattern of multiple HIF-1 α –mediated genes involved in adhesion formation 38 in the early postoperative peritoneum. These include plasminogen activator inhibitor-1, 36 VEGF and its receptor, 20 and tissue factor.…”

Section: Discussionsupporting

confidence: 59%

Combined intraoperative administration of a histone deacetylase inhibitor and a neurokinin-1 receptor antagonist synergistically reduces intra-abdominal adhesion formation in a rat model

Cassidy

Sherburne

Heydrick

et al. 2015

Surgery

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Background Intra-abdominal adhesions are the most frequent postoperative complication after abdominopelvic surgery. Our laboratory has previously shown that an intraoperative peritoneal lavage containing either the histone deacetylase inhibitor valproic acid (VPA) or a neurokinin-1 receptor antagonist (NK-1RA) reduced adhesions by approximately 50%in a rat model. The objective of this study was to determine whether the combination of these 2 drugs was more effective in reducing adhesions than either alone. Methods Rats underwent laparotomy with creation of peritoneal ischemic buttons to induce adhesions. A single dose of VPA (25 mg/kg), NK-1RA (50 mg/kg), a combination of both, or 0.9% saline was lavaged intraperitoneally just before wound closure. On postoperative day 7, adhesions were quantified. To investigate early mechanisms of adhesiogenesis, adhesions were created as described and adhesive button tissue was harvested at 30 minutes and 3 hours postoperatively and fibrinogen and vascular endothelial growth factor (VEGF) protein levels, both indices of peritoneal extravasations, were determined by Western blot analysis. Peritoneal fluid was collected in similar experiments at 30 minutes, and 3 and 6 hours to measure fibrinolytic activity, an index of the ability of the peritoneum to degrade fibrinous adhesions. Results The coadministration of VPA plus NK-1RA reduces adhesions by 72.6% relative to saline (P < .001); this reduction was greater than either compound alone (P < .001). Peritoneal fibrinolytic activity was significantly increased at 3 and 6 hours postoperatively in animals administered the combination therapy versus saline (P = .01). VPA plus NK-1RA significantly decreased fibrinogen and VEGF protein levels at 3 and 6 hours compared with saline controls. Conclusion These results suggest that a combined pharmacologic approach targeting multiple adhesiogenic pathways provides optimal adhesion prevention.

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“…The pathogenesis of adhesion formation involves three important trauma-induced processes: (I) inhibition of the fibrinolytic and extracellular matrix degradation systems [34,35]; (II) induction of an inflammatory response involving the production of cytokines and growth factor-β (TGF-β1), a key regulator of tissue fibrosis [36-38]; and (III) induction of tissue hypoxia following interruption of blood delivery to mesothelial cells and sub-mesothelial fibroblasts, leading to increased expression of hypoxia-induced factor-1α [39,40] and vascular endothelial growth factor, responsible for collagen formation and angiogenesis [31,41]. …”

Section: Articlementioning

confidence: 99%

Peritoneal adhesion index (PAI): proposal of a score for the “ignored iceberg” of medicine and surgery

et al. 2013

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Peritoneal adhesions describe a condition in which pathological bonds form between the omentum, the small and large bowels, the abdominal wall, and other intra-abdominal organs. Different classification systems have been proposed, but they do not resolve the underlying problem of ambiguity in the quantification and definition of adhesions. We therefore propose a standardized classification system of adhesions to universalize their definition based on the macroscopic appearance of adhesions and their diffusion to different regions of the abdomen. By scoring with these criteria, the peritoneal adhesion index (PAI) can range from 0 to 30, unambiguously specifying precise adhesion scenarios. The standardized classification and quantification of adhesions would enable different studies to more meaningfully integrate their results, thereby facilitating a more comprehensive approach to the treatment and management of this pathology.

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RNA Interference Targeting Hypoxia Inducible Factor 1α Reduces Post-Operative Adhesions in Rats

Cited by 38 publications

References 40 publications

Variation in stability of housekeeping genes in healthy and adhesion-related mesothelium

Variation in stability of housekeeping genes in healthy and adhesion-related mesothelium

Combined intraoperative administration of a histone deacetylase inhibitor and a neurokinin-1 receptor antagonist synergistically reduces intra-abdominal adhesion formation in a rat model

Peritoneal adhesion index (PAI): proposal of a score for the “ignored iceberg” of medicine and surgery

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