Expression of cyclooxygenase genes in the jejunum of horses during low-flow ischemia and reperfusion

Hilton, Hugo G.; Nieto, Jorge E.; Moore, Peter F.; Harmon, Faye A.; Naydan, Diane K.; Snyder, Jack R.

doi:10.2460/ajvr.72.5.681

Cited by 11 publications

(14 citation statements)

References 34 publications

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“…Recovery of sufficient perfusion may facilitate correction of these changes. Depending on the duration of the ischemic period, reperfusion may result in delivery of toxic oxygen metabolites and free radicals created from hypoxanthine and ß-actin, which may be more severe than those during the ischemic period [1,3,4].…”

Section: Introductionmentioning

confidence: 99%

Assessment of effects of methylene blue on intestinal ischemia and reperfusion in a rabbit model: hemodynamic, histological and immunohistochemical study

et al. 2020

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Background: Intestinal ischemia-reperfusion (IR) is an important clinical occurrence seen in common diseases, such as gastric dilatation-volvulus in dogs or colic in horses. Limited data is available on the use of methylene blue in veterinary medicine for intestinal ischemia-reperfusion. The present study aimed to compare the hemodynamic, histopathological, and immunohistochemical effects of two doses of methylene blue in two rabbit model groups In one group, 5 mg/kg IV was administered, and in another, 20 mg/kg IV was administered following a constant rate infusion (CRI) of 2 mg/kg/h that lasted 6 h. All the groups, including a control group had intestinal ischemiareperfusion. Immunohistochemical analysis was performed using caspase-3. Results: During ischemia, hemodynamic depression with reduced perfusion and elevated lactate were observed. During reperfusion, methylene blue (MB) infusion generated an increase in cardiac output due to a positive chronotropic effect, an elevation of preload, and an intense positive inotropic effect. The changes in heart rate and blood pressure were significantly greater in the group in which methylene blue 5 mg/kg IV was administered (MB5) than in the group in which methylene blue 20 mg/kg IV dose was administered (MB20). In addition, lactate and stroke volume variations were significantly reduced, and vascular resistance was significantly elevated in the MB5 group compared with the control group and MB20 group. The MB5 group showed a significant decrease in the intensity of histopathological lesion scores in the intestines and a decrease in caspase-3 areas, in comparison with other groups. Conclusions: MB infusion produced improvements in hemodynamic parameters in rabbits subjected to intestinal IR, with increased cardiac output and blood pressure. An MB dosage of 5 mg/kg IV administered at a CRI of 2 mg/ kg/h exhibited the most protective effect against histopathological damage caused by intestinal ischemiareperfusion. Further studies with MB in clinical veterinary pathologies are recommended to fully evaluate these findings.

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Section: Introductionmentioning

confidence: 99%

Assessment of effects of methylene blue on intestinal ischemia and reperfusion in a rabbit model: hemodynamic, histological and immunohistochemical study

et al. 2020

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“…Unlike COX-1, which is constitutively expressed throughout the body, COX-2 is primarily an inducible enzyme which increases in response to growth factors and inflammatory stimuli such as LPS. In horses, constitutive expression of COX-2 has been demonstrated in the glandular mucosa of the stomach (Morrissey, Bellenger, Ryan, & Baird, 2010;Nieto, Aleman, Anderson, Fiack, & Snyder, 2012), mucosa of the urinary bladder (Nieto et al, 2012), jejunum (Cook et al, 2009;Hilton et al, 2011), and left dorsal colon (Morton et al, 2009). Higher COX-2 expression in these tissues is likely beneficial as PGE 2 promotes local inflammation and cytotoxic immune responses to prevent pathogen entry (Kalinski, 2012).…”

Section: Discussionmentioning

confidence: 99%

In vitro anti‐LPS dose determination of ketorolac tromethamine and in vivo safety of repeated dosing in healthy horses

Bianco

Moore

Cooper

et al. 2017

Vet Pharm & Therapeutics

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Flunixin meglumine (FM) is a commonly used Nonsteroidal anti-inflammatory drug (NSAID) in horses, but clinical efficacy is often unsatisfactory. Ketorolac tromethamine (KT) demonstrates superior efficacy compared to other NSAIDs in humans, but its anti-inflammatory effects have not been investigated in the horse. Safety of repeated dosing of KT has not been evaluated. The first objective was to conduct a dose determination study to verify that a previously described dosage of KT would inhibit Lipopolysaccharide (LPS)-induced eicosanoid production in vitro, and to compare KT effects of this inhibition to those of FM. Then, a randomized crossover study was performed using nine healthy horses to evaluate plasma concentrations of KT and FM following IV administration. Administered dosages of KT and FM were 0.5 mg/kg and 1.1 mg/kg, respectively. Safety following six repeated doses of KT was assessed.Ketorolac tromethamine and FM suppressed LPS-induced Thromboxane B 2 (TXB 2 ) and Prostaglandin E 2 (PGE 2 ) production in vitro for up to 12 hr. Intravenous administration produced plasma concentrations of KT and FM similar to previous reports. No adverse effects were observed. A KT dosage of 0.5 mg/kg IV inhibited LPS-induced eicosanoids in vitro, and repeated dosing for up to 3 days appears safe in healthy horses. Investigation of in vivo anti-inflammatory and analgesic effects of KT is warranted.

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“…In the equine jejunum, Cox 1 protein is constitutively expressed and is increased, as is Cox 2, at 18 hours reperfusion following a two hour ischemic period [10, 20]. Transcription of Cox 1 also increased, although not significantly, in response to 75 minutes of reduced blood flow to the jejunum [15]. Cox 1 is constitutively expressed in the lamina propria of equine colon and IR significantly increases protein levels in the epithelial cells [9, 11].…”

Section: Ischemia/reperfusionmentioning

confidence: 99%

Membrane lipid interactions in intestinal ischemia/reperfusion-induced Injury

Slone

Fleming

2014

Clinical Immunology

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Ischemia, lack of blood flow, and reperfusion, return of blood flow, is a common phenomenon affecting millions of Americans each year. Roughly 30,000 Americans per year experience intestinal ischemia-reperfusion (IR), which is associated with a high mortality rate. Previous studies of the intestine established a role for neutrophils, eicosanoids, the complement system and naturally occurring antibodies in IR-induced pathology. Furthermore, data indicate involvement of a lipid or lipid-like moiety in mediating IR-induced damage. It has been proposed that exposure of neo-antigens are recognized by antibodies, triggering action of the complement cascade. While it is evident that the pathophysiology of IR-induced injury is complex and multi-factorial, we focus this review on the involvement of eicosanoids, phospholipids and neo-antigens in the early pathogenesis. Lipid changes occurring in response to IR, neo-antigens exposed and the role of a phospholipid transporter, phospholipid scramblase 1 will be discussed.

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Expression of cyclooxygenase genes in the jejunum of horses during low-flow ischemia and reperfusion

Abstract: Low-flow ischemia resulted in upregulation of COX-2 gene expression in the jejunum of horses. Housekeeping genes traditionally used as internal standards may not be stable in this tissue during arterial low-flow ischemia and reperfusion.

Cited by 11 publications

References 34 publications

Assessment of effects of methylene blue on intestinal ischemia and reperfusion in a rabbit model: hemodynamic, histological and immunohistochemical study

Assessment of effects of methylene blue on intestinal ischemia and reperfusion in a rabbit model: hemodynamic, histological and immunohistochemical study

In vitro anti‐LPS dose determination of ketorolac tromethamine and in vivo safety of repeated dosing in healthy horses

Membrane lipid interactions in intestinal ischemia/reperfusion-induced Injury

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