Abbate Antonio, Salloum Fadi N, Ockaili Ramzi A, Fowler Alpha A, Biondi-Zoccai Giuseppe G L, Straino Stefania, Lipinski Michael J, Baldi Alfonso, Crea Filippo, Biasucci Luigi M, Vetrovec George W, Kukreja Rakesh C
Virginia Commonwealth University Pauley Heart Center, Richmond, VA 23233, USA.
J Cardiovasc Pharmacol. 2007 Jun;49(6):416-8. doi: 10.1097/FJC.0b013e31804a5e50.
To assess changes in cardiac function in animals with ischemic congestive heart failure (CHF) treated with a selective cyclo-oxygenase-2 (COX-2) inhibitor.
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.
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.
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.
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.
评估用选择性环氧化酶-2（COX-2）抑制剂治疗的缺血性充血性心力衰竭（CHF）动物的心脏功能变化。
在CHF患者中，COX-2表达与心力衰竭恶化特征相关。然而，缺乏COX-2抑制对缺血性CHF功能有益或有害影响的证据。
30只雄性Wistar大鼠接受冠状动脉结扎，并使其恢复12个月。5只假手术动物用作对照。12个月后，6只存活动物接受基线超声心动图检查，以测量舒张末期直径（EDD）、收缩末期直径（ESD）、缩短分数（FS）以及前后舒张期和收缩期壁厚。此后，动物每天接受腹腔注射帕瑞昔布（0.75mg/kg），持续7天。在第7天，进行重复超声心动图检查。
与基线相比，帕瑞昔布治疗7天后的重复超声心动图显示EDD无变化（9.4±0.4mm对9.4±0.3mm，P = 0.9），ESD显著降低（5.5±0.8mm对6.4±0.3mm，P = 0.028），FS显著改善（43±3%对32±5%，P = 0.027）。FS的改善与梗死区收缩期厚度的显著变化相关（3.6±0.4mm对3.0±0.1mm，P = 0.046），而在远隔区域未观察到收缩期厚度的显著变化。
在缺血性CHF中给予帕瑞昔布可使梗死周边心肌的功能得到改善。这一发现可能对改善缺血性心脏病患者的生活质量乃至生存率有用。
