Cyclooxygenase-2 inhibition increases mortality, enhances left ventricular remodeling, and impairs systolic function after myocardial infarction in the pig

Article

关键词: ATHEROSCLEROTIC LESION FORMATION;    IMPROVES CARDIAC-FUNCTION;    ISCHEMIA/REPERFUSION INJURY;    ENDOTHELIAL FUNCTION;    COX-2 INHIBITION;    LATE-PHASE;    CELECOXIB;    VOLUME;    CONDUCTANCE;    DEFICIENT;   

DOI  :  10.1161/CIRCULATIONAHA.106.647230

来源: SCIE

【 摘 要 】

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/mm(2); 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.

【 授权许可】

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