on January 8, 2007
Published online before print January 8, 2007, doi: 10.1161/CIRCULATIONAHA.106.647230
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Submitted on June 21, 2006
From the Department of Cardiology, UMC Utrecht (L.T., J.P.G.S., C.W.J.V., M.J.C., M.E., C.S., P.F.G., C.B., G.P., D.P.V.d.K.), Utrecht, the Netherlands; Department of Cardiology, Leiden UMC (P.S.), Leiden, the Netherlands; Department of Cardiology, AMC Amsterdam (L.T., J.J.P.), Amsterdam, the Netherlands; Genome Institute of Singapore (S.K.S., L.H.), Genome, Singapore; and Interuniversity Cardiology Institute of the Netherlands (J.P.G.S., D.P.V.d.K.), Utrecht, the Netherlands. * To whom correspondence should be addressed. E-mail: d.dekleijn{at}umcutrecht.nl.
Background--Cyclooxygenase (COX)-2 expression in the heart increases after myocardial infarction (MI). In murine models of MI, COX-2 inhibition preserves left ventricular dimensions and function. We studied the effect of selective COX-2 inhibition on left ventricular remodeling and function after MI in a pig model. Methods and Results--Twenty-two pigs were assigned to COX-2 inhibition with a COX-2 inhibitor (COX-2i; celecoxib 400 mg twice daily; n=14) or a control group (n=8). MI was induced by left circumflex coronary artery ligation, and the animals were euthanized 6 weeks later. Cardiac dimensions and function were assessed with echocardiography and conductance catheters. Infarct size and collagen density were analyzed with triphenyltetrazolium chloride staining and picrosirius red staining, respectively. COX-2 inhibition increased mortality compared with controls (50% versus 0%, P=0.022), whereas infarct size was similar (13.1±0.7% versus 14.1±0.1%, P=0.536). The decrease in thickness of the infarcted myocardial wall was more pronounced in the COX-2i group (60.6±9.6% versus 36.2±5.7%, P=0.001). End-diastolic volume was higher in the COX-2i group (133.9±33.5 versus 91.1±24.0 mL; P=0.021), as was the end-systolic volume at 100 mm Hg (81.7±27.8 versus 56.3±21.1 mL; P=0.037), which indicates that systolic function was more severely impaired. Infarct collagen density was lower after COX-2i treatment (25.3±3.9 versus 56.1±23.8 gray value/mm2; P=0.005). Conclusions--In pigs, COX-2 inhibition after MI is associated with increased mortality, enhanced left ventricular remodeling, and impaired systolic function, probably due to decreased infarct collagen fiber density.
Accepted on October 31, 2006
Cyclooxygenase-2 Inhibition Increases Mortality, Enhances Left Ventricular Remodeling, and Impairs Systolic Function After Myocardial Infarction in the Pig
Leo Timmers MD,
Key words: myocardial infarction • heart failure • remodeling • enzymes
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