Protective effects of parecoxib, a cyclo-oxygenase-2 inhibitor, in postinfarction remodeling in the rat.
OBJECTIVE
Selective cyclo-oxygenase-2 (COX-2) inhibitors have been shown to preserve hemodynamic performance in experimental models of acute myocardial infarction (AMI) in rodents. The impact of COX-2 inhibition on apoptosis, vascular density, and postinfarction remodeling has not yet been fully characterized. The aim of the present study was to evaluate the effects of parecoxib, a selective COX-2 inhibitor, in an experimental AMI model in the rat.


METHODS
Twenty-four male Wistar rats (10 weeks of age, weighing 350-500 g) underwent surgical left coronary artery ligation. Four animals died within 24 hours. Starting on day 2, 10 rats received parecoxib (0.75 mg/kg intraperitoneal) daily for 5 days and the remaining 10 received NaCl-0.9%. Animals underwent transthoracic echocardiography before surgery and 7 days later for the measurement of end-diastolic and end-systolic diameter and wall thickness; thereafter, animals were sacrificed and histological analysis was performed to evaluate cardiomyocyte apoptosis and small arteriolar density. Data are expressed as mean and standard error.


RESULTS
Three saline-treated (30%) and zero parecoxib-treated animals died before day 7. Compared with saline-treated animals, rats treated with parecoxib had a smaller end-diastolic diameter (6.3 +/- 0.1 vs. 7.0 +/- 0.1 mm, P = 0.018) and end-systolic diameter (2.7 +/- 0.1 vs. 3.9 +/- 0.1 mm, P = 0.027), and had a greater fractional shortening (57 +/- 1 vs. 45 +/- 2%, P = 0.050). Systolic thickness in the anterior (infarct) wall was also significantly greater in the parecoxib-treated animals (3.2 +/- 0.1 vs. 2.7 +/- 0.1 mm, P = 0.008), while the posterior wall was not significantly affected (P = 0.08). Aneurysmal dilatation of the left ventricle was more frequent in saline-treated versus parecoxib-treated animals (43 vs. 0%, P = 0.025). Parecoxib treatment was associated with lower apoptotic rates (1.0 +/- 0.2 vs. 4.0 +/- 0.4%, P < 0.001) and preservation of arteriolar density (20 +/- 5 vs. 8 +/- 2 mm/mm3, P = 0.018) in the peri-infarct area, without differences in circulating interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma levels.


CONCLUSIONS
Administration of parecoxib significantly ameliorates the remodeling process after AMI, possibly through prevention of apoptosis and preservation of myocardial vascularity. These findings aid in the understanding of the role of COX-2 in ischemic damage and remodeling.
Straino
Stefania
S
VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
Salloum
Fadi N
FN
Baldi
Alfonso
A
Ockaili
Ramzi A
RA
Piro
Maddalena
M
Das
Anindita
A
Qureshi
Ian Z
IZ
Biasucci
Luigi M
LM
Capogrossi
Maurizio C
MC
Biondi-Zoccai
Giuseppe G L
GG
Severino
Anna
A
Mellone
Pasquale
P
Crea
Filippo
F
Vetrovec
George W
GW
Kukreja
Rakesh C
RC
Abbate
Antonio
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001160:Arterioles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D004452:Echocardiography; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016019:Survival Analysis; D020257:Ventricular Remodeling / Q000187:drug effects*
D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D007555:Isoxazoles; C409945:parecoxib