Cited 72 times since 2007 (4.1 per year) source: EuropePMC Circulation, Volume 115, Issue 3, 8 2 2007, Pages 326-332 Cyclooxygenase-2 inhibition increases mortality, enhances left ventricular remodeling, and impairs systolic function after myocardial infarction in the pig. Timmers L, Sluijter JP, Verlaan CW, Steendijk P, Cramer MJ, Emons M, Strijder C, Gründeman PF, Sze SK, Hua L, Piek JJ, Borst C, Pasterkamp G, de Kleijn DP
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.
