Improvement of cardiac function with parecoxib, a cyclo-oxygenase-2 inhibitor, in a rat model of ischemic heart failure.
OBJECTIVE
To assess changes in cardiac function in animals with ischemic congestive heart failure (CHF) treated with a selective cyclo-oxygenase-2 (COX-2) inhibitor.


BACKGROUND
In patients with CHF, COX-2 expression was associated with features of worsening failure. However, evidence of beneficial or detrimental functional effects of COX-2 inhibition in ischemic CHF is lacking.


METHODS
Thirty male Wistar rats underwent coronary ligation and were allowed to recover for 12 months. Five sham-operated animals were used as controls. After 12 months, six surviving animals underwent baseline echocardiogram to measure end-diastolic diameter (EDD), end-systolic diameters (ESD), fractional shortening (FS), and anterior and posterior diastolic and systolic wall thicknesses. The animals were thereafter treated by daily intraperitoneal parecoxib injections (0.75 mg/kg) for 7 days. On day 7, a repeat echocardiogram was performed.


RESULTS
When compared to baseline, repeat echocardiography after 7 days of parecoxib treatment showed no changes in the EDD (9.4 +/- 0.4 mm vs. 9.4 +/- 0.3 mm, P = 0.9), a significant reduction of ESD (5.5 +/- 0.8 mm vs. 6.4 +/- 0.3 mm, P = 0.028), and a significant improvement in the FS (43 +/- 3% vs. 32 +/- 5%, P = 0.027). Improvement of FS was associated with a significant change in systolic thickness in the infarct zone (3.6 +/- 0.4 mm vs. 3.0 +/- 0.1 mm, P = 0.046), whereas no significant changes in systolic thickness in the remote area were observed.


CONCLUSIONS
Administration of parecoxib in ischemic CHF provides functional improvement of the peri-infarct myocardium. This finding may prove useful in improving quality of life and, perhaps, survival in patients with ischemic heart disease.
Abbate
Antonio
A
Virginia Commonwealth University Pauley Heart Center, Richmond, VA 23233, USA. abbatea@yahoo.com
Salloum
Fadi N
FN
Ockaili
Ramzi A
RA
Fowler
Alpha A
AA
Biondi-Zoccai
Giuseppe G L
GG
Straino
Stefania
S
Lipinski
Michael J
MJ
Baldi
Alfonso
A
Crea
Filippo
F
Biasucci
Luigi M
LM
Vetrovec
George W
GW
Kukreja
Rakesh C
RC
D000818:Animals; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004452:Echocardiography; D006333:Heart Failure / Q000209:etiology / Q000517:prevention & control*; D006334:Heart Function Tests; D007555:Isoxazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D052246:Cyclooxygenase 2 Inhibitors; D007555:Isoxazoles; C409945:parecoxib; D051546:Cyclooxygenase 2