title: Cyclooxygenase-2 inhibition increases mortality, enhances left ventricular remodeling, and impairs systolic function after myocardial infarction in the pig.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Leo
authors.initials: L
authors.lastname: Timmers
authors.forename: Joost P G
authors.initials: JP
authors.lastname: Sluijter
authors.forename: Cees W J
authors.initials: CW
authors.lastname: Verlaan
authors.forename: Paul
authors.initials: P
authors.lastname: Steendijk
authors.forename: Maarten Jan
authors.initials: MJ
authors.lastname: Cramer
authors.forename: Maringa
authors.initials: M
authors.lastname: Emons
authors.forename: Chaylendra
authors.initials: C
authors.lastname: Strijder
authors.forename: Paul F
authors.initials: PF
authors.lastname: Gründeman
authors.forename: Siu Kwan
authors.initials: SK
authors.lastname: Sze
authors.forename: Lin
authors.initials: L
authors.lastname: Hua
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Piek
authors.forename: Cornelius
authors.initials: C
authors.lastname: Borst
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000473:pathology; D000068579:Celecoxib; D003094:Collagen / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D009203:Myocardial Infarction / Q000201:enzymology* / Q000401:mortality; D011720:Pyrazoles / Q000009:adverse effects* / Q000494:pharmacology; D012307:Risk Factors; D013449:Sulfonamides / Q000009:adverse effects* / Q000494:pharmacology; D013552:Swine; D013599:Systole / Q000187:drug effects / Q000502:physiology*; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D003094:Collagen; D051546:Cyclooxygenase 2; D000068579:Celecoxib