Inhibition of cyclo-oxygenase-2 exacerbates ischaemia-induced acute myocardial dysfunction in the rabbit

British Journal of Pharmacology
Giuseppe RossoniJ L Wallace

Abstract

1. The effects of treatment with a number of cyclo-oxygenase inhibitors, (celecoxib, meloxicam, DuP-697 and aspirin) on ischaemia-reperfusion-induced myocardial dysfunction were examined using an in vitro perfused rabbit heart model. 2. Ischaemia resulted in myocardial dysfunction, as indicated by a significant increase in left ventricular end diastolic pressure and marked changes in coronary perfusion pressure and left ventricular developed pressure. In the post-ischaemic state, coronary perfusion pressure increased dramatically, left ventricular developed pressure recovered to a small degree and there were significant increases in creatinine kinase release (indicative of myocardial damage) and prostacyclin release. 3. Pretreatment with aspirin, or with drugs that selectively inhibit cyclo-oxygenase-2 (celecoxib, meloxicam and DuP-697), resulted in a concentration-dependent exacerbation of the myocardial dysfunction and damage. Exacerbation of myocardial dysfunction and damage was evident with 10 microM concentrations of the cyclo-oxygenase-2 inhibitors, which inhibited prostacyclin release but did not affect cyclo-oxygenase-1 activity (as measured by whole blood thromboxane synthesis). 4. NCX-4016, a nitric oxide-releasing as...Continue Reading

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Citations

Apr 3, 2002·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·J L Wallace
Jul 9, 2003·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·P GreseleA M Mezzasoma
Sep 5, 2002·British Journal of Pharmacology·Giuseppe RossoniFerruccio Berti
Jan 4, 2012·Clinical and Experimental Pharmacology & Physiology·Ming ZhaoWei-Jin Zang
May 9, 2002·Expert Opinion on Investigational Drugs·Ian L Megson, David J Webb
Sep 2, 2010·The Journal of Thoracic and Cardiovascular Surgery·Michael P RobichFrank W Sellke
Aug 19, 2008·The Journal of Surgical Research·Jonathan McGuinnessJ Mark Redmond
Dec 18, 2007·The American Journal of Emergency Medicine·Hector LozanoJose A Adams
Mar 5, 2016·Expert Opinion on Investigational Drugs·Nikolaos PapageorgiouDimitris Tousoulis
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Jul 18, 2002·Nature Reviews. Drug Discovery·John L WallaceStefano Fiorucci
Feb 18, 2003·Fundamental & Clinical Pharmacology·John L Wallace, Piero Del Soldato
Jan 22, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yoshitaka IwanagaJohn Ross
May 13, 2006·Molecular and Cellular Biochemistry·Elena C LascanoJorge A Negroni

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