|Effects of selective cyclooxygenase-2 and nonselective cyclooxygenase inhibition on ischemic myocardium.|
|PMID: 20804993 Owner: NLM Status: MEDLINE|
|OBJECTIVE: We explored effects of nonselective cyclooxygenase and selective cyclooxygenase 2 inhibition on collateral development in a model of chronic myocardial ischemia. We hypothesized that cyclooxygenase 2 inhibitors would 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 3 groups and given no drug (control, n = 7), a nonselective cyclooxygenase inhibitor (naproxen 400 mg daily, n = 7), or a selective cyclooxygenase 2 inhibitor (celecoxib 200 mg daily, 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 celecoxib group demonstrated significantly increased mean arterial pressure and decreased left ventricular function. Myocardial perfusion in the celecoxib group was similar to control value but less than in the naproxen group. Coronary microvascular contraction in the collateral-dependent territory was increased in the naproxen group but minimally affected in the celecoxib group. Oxidative stress and apoptosis were increased in the celecoxib group. Expression of angiogenic markers vascular endothelial growth factor and phospho-endothelial nitric oxide synthase (ser1177) and tissue levels of prostacyclin were decreased in both celecoxib and naproxen groups. The naproxen group had diminished endostatin expression.
CONCLUSIONS: Selective and nonselective cyclooxygenase inhibition are more complex in effect than previously published, but they did not decrease collateral-dependent blood flow to the myocardium in our model of chronic myocardial ischemia.
|Michael P Robich; Louis M Chu; Jun Feng; Thomas A Burgess; Roger J Laham; Cesario Bianchi; Frank W Sellke|
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|Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't|
|Title: The Journal of thoracic and cardiovascular surgery Volume: 140 ISSN: 1097-685X ISO Abbreviation: J. Thorac. Cardiovasc. Surg. Publication Date: 2010 Nov|
|Created Date: 2010-10-18 Completed Date: 2010-11-08 Revised Date: 2014-09-24|
Medline Journal Info:
|Nlm Unique ID: 0376343 Medline TA: J Thorac Cardiovasc Surg Country: United States|
|Languages: eng Pagination: 1143-52 Citation Subset: AIM; IM|
|Copyright © 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.|
|APA/MLA Format Download EndNote Download BibTex|
Apoptosis / drug effects
Blood Pressure / drug effects
Collateral Circulation / drug effects
Coronary Circulation / drug effects*
Cyclooxygenase 2 / metabolism*
Cyclooxygenase 2 Inhibitors / toxicity*
Cyclooxygenase Inhibitors / toxicity*
Disease Models, Animal
Dose-Response Relationship, Drug
Heart Rate / drug effects
Inflammation Mediators / metabolism
Microcirculation / drug effects
Myocardial Ischemia / diagnosis, enzymology*, physiopathology
Myocardial Perfusion Imaging
Myocardium / enzymology*, pathology
Naproxen / toxicity*
Neovascularization, Physiologic / drug effects
Oxidative Stress / drug effects
Prostaglandins / metabolism
Pyrazoles / toxicity*
Sulfonamides / toxicity*
Vasoconstrictor Agents / pharmacology
Vasodilator Agents / pharmacology
Ventricular Function, Left / drug effects
|5T32-HL0074/HL/NHLBI NIH HHS; R01 HL046716/HL/NHLBI NIH HHS; R01 HL069024/HL/NHLBI NIH HHS; R01 HL085647/HL/NHLBI NIH HHS; R01HL46716/HL/NHLBI NIH HHS; R01HL69024/HL/NHLBI NIH HHS; R01HL85647/HL/NHLBI NIH HHS; T32 HL076130/HL/NHLBI NIH HHS|
|0/Angiogenic Proteins; 0/Cyclooxygenase 2 Inhibitors; 0/Cyclooxygenase Inhibitors; 0/Inflammation Mediators; 0/Prostaglandins; 0/Pyrazoles; 0/Sulfonamides; 0/Vasoconstrictor Agents; 0/Vasodilator Agents; 169590-42-5/celecoxib; 57Y76R9ATQ/Naproxen; EC 188.8.131.52/Cyclooxygenase 2|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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