Improvement of cardiac function with parecoxib, a cyclo-oxygenase-2 inhibitor, in a rat model of ischemic heart failure

J Cardiovasc Pharmacol. 2007 Jun;49(6):416-8. doi: 10.1097/FJC.0b013e31804a5e50.

Abstract

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.

MeSH terms

  • Animals
  • Cyclooxygenase 2 / biosynthesis
  • Cyclooxygenase 2 Inhibitors / administration & dosage
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Cyclooxygenase 2 Inhibitors / therapeutic use*
  • Disease Models, Animal
  • Echocardiography
  • Heart Failure / etiology
  • Heart Failure / prevention & control*
  • Heart Function Tests
  • Isoxazoles / administration & dosage
  • Isoxazoles / pharmacology
  • Isoxazoles / therapeutic use*
  • Male
  • Myocardial Ischemia / complications*
  • Myocardium* / enzymology
  • Myocardium* / pathology
  • Rats
  • Rats, Wistar

Substances

  • Cyclooxygenase 2 Inhibitors
  • Isoxazoles
  • parecoxib
  • Cyclooxygenase 2