| Proinflammatory events in right ventricular damage during pulmonary embolism: effects of treatment with ketorolac in rats. | |
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MedLine Citation:
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PMID: 19620882 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Right ventricular (RV) damage contributes to poor clinical outcome after pulmonary embolism (PE). Our studies show that neutrophils contribute to RV dysfunction in rat PE. Present studies examine effects of the nonsteroidal anti-inflammatory drug, ketorolac, upon RV inflammation and dysfunction. RV inflammatory gene expression significantly increased 6 and 18 hours after PE [cytokine-induced neutrophil chemoattractant-1 (CINC-1) 18-fold and 24-fold; cyclooxygenase-2 21-fold and 32-fold]. Eighteen hours after PE, there was significant upregulation of adhesion molecules (selectin E 18-fold; intercellular adhesion molecule 1 14-fold), influx of neutrophils (myeloperoxidase activity 21-fold), depressed RV function (RV peak systolic pressure = 24 +/- 3 vs. 40 +/- 1 mm Hg; maximum rate of pressure development = 444 +/- 79 vs. 1533 +/- 146; maximum rate of pressure decrease = -357 +/- 50 vs. -651 +/- 44), and release of cardiac troponin I (7.8 +/- 1.9 ng/mL) compared with vehicle. Ketorolac (10 mg/kg, intraperitoneally) significantly reduced expression of CINC-1, cyclooxygenase-2, selectin E, and intercellular adhesion molecule 1, lowered neutrophil influx, improved RV function (RV peak systolic pressure was 34 +/- 3 mm Hg; maximum rate of pressure development = 1288 +/- 146; maximum rate of pressure decrease = -611 +/- 92), and marginally reduced cardiac troponin I release (P < 0.07) compared with PE alone. Ketorolac reduced CINC-1 stimulated chemotaxis of isolated neutrophils. PE converted cardiac tissue into a proinflammatory phenotype. Ketorolac reduced RV inflammatory genes, reduced neutrophil influx, and improved RV function in rat PE. |
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Authors:
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John A Watts; Michael A Gellar; Lori K Stuart; Maria Obraztsova; Jeffrey A Kline |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 54 ISSN: 1533-4023 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2010-05-06 Completed Date: 2010-08-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 246-52 Citation Subset: IM |
Affiliation:
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Emergency Medicine Research, Carolinas Medical Center, Charlotte, NC 28232-2861, USA. jwatts@carolinas.org |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Inflammatory Agents, Non-Steroidal / therapeutic use* Chemokine CXCL1 / genetics, metabolism Cyclooxygenase 2 / genetics, metabolism Cyclooxygenase Inhibitors / therapeutic use E-Selectin / genetics, metabolism Gene Expression Regulation / drug effects Inflammation / drug therapy*, physiopathology* Intercellular Adhesion Molecule-1 / genetics, metabolism Ketorolac / therapeutic use* Male Myocardial Contraction / drug effects Neutrophil Infiltration / drug effects Peroxidase / metabolism Pulmonary Embolism / physiopathology* RNA, Messenger / metabolism Rats Rats, Sprague-Dawley Time Factors Troponin I / metabolism Ventricular Dysfunction, Right / metabolism, physiopathology* Ventricular Pressure / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents, Non-Steroidal; 0/Chemokine CXCL1; 0/Cxcl1 protein, rat; 0/Cyclooxygenase Inhibitors; 0/E-Selectin; 0/RNA, Messenger; 0/Troponin I; 126547-89-5/Intercellular Adhesion Molecule-1; 66635-83-4/Ketorolac; EC 1.11.1.7/Peroxidase; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/Ptgs2 protein, rat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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