Mercanoğlu Güldem Olguner, Pamukçu Burak, Safran Nurhas, Mercanoğlu Fehmi, Fici Francesco, Güngör Mehmet
Department of Pharmacology, Faculty of Pharmacy, Yeditepe University, Istanbul, Turkey.
Anadolu Kardiyol Derg. 2010 Feb;10(1):18-27.
Ventricular remodeling (VR) which develops after myocardial infarction (MI) plays an important role in progressive left ventricular dysfunction. We aimed to investigate the role of nebivolol treatment on VR after a MI in a rat ischemia-reperfusion model.
Rats were divided into 3 groups of 12 each: sham operated (sham-control), MI-induced (MI-control) and nebivolol treated (MI-nebivolol). Left ventricular (LV) diameters, volumes, and diastolic filling parameters were evaluated by echocardiography. On the 28th day, after recording the systemic and LV pressures and determining the plasma nitric oxide (NO) and peroxynitrite (ONOO-) levels , animals were sacrificed and heart, body and LV weights (HW, BW, LVW) were measured and infarct sizes were determined. Results were evaluated statistically by ANOVA for repeated measurements 3x3 factorial design with post-hoc Bonferroni test.
After MI, while VR (an increase in LV diameters and volumes associated with a decrease in EF, FS and posterior wall thickness change (LWPc) was significant in MI-control rats (p<0.05 for; all comparisons) these changes were significantly less in MI-nebivolol group (p=0.08 and p=0.06 for EF and FS respectively). LV end diastolic pressure (LVEDP) was lower (p<0.005) and Delta+/- dp/dt's (p<0.05) were higher in MI-nebivolol group compared to MI-control animals. Although infarct sizes were similar in MI-induced groups (p=0.79); LVW/HW and HW/BW's were significantly greater in the MI-control group compared to sham-control (p<0.01 for all comparisons), these changes were not statistically significant in MI-nebivolol group. The increase in plasma NO and ONOO- levels were also prevented with nebivolol.
Nebivolol therapy reduced the effects of VR in rats after MI. These beneficial effects were not related to its heart rate and blood pressure reducing effects. Nitric oxide regulatory action of this compound may contribute these beneficial effects on VR developed after MI.
心肌梗死（MI）后发生的心室重构（VR）在进行性左心室功能障碍中起重要作用。我们旨在研究奈必洛尔治疗在大鼠缺血再灌注模型中对MI后VR的作用。
将大鼠分为3组，每组12只：假手术组（假手术对照）、MI诱导组（MI对照）和奈必洛尔治疗组（MI-奈必洛尔）。通过超声心动图评估左心室（LV）直径、容积和舒张期充盈参数。在第28天，记录全身和LV压力并测定血浆一氧化氮（NO）和过氧亚硝酸盐（ONOO-）水平后，处死动物并测量心脏、体重和LV重量（HW、BW、LVW），并确定梗死面积。结果采用重复测量的三因素方差分析（3×3析因设计）和事后Bonferroni检验进行统计学评估。
MI后，MI对照大鼠的VR（LV直径和容积增加，同时EF、FS和后壁厚度变化（LWPc）降低）显著（所有比较p<0.05），而MI-奈必洛尔组的这些变化明显较小（EF和FS分别为p=0.08和p=0.06）。与MI对照动物相比，MI-奈必洛尔组的LV舒张末期压力（LVEDP）较低（p<0.005），Delta+/- dp/dt较高（p<0.05）。虽然MI诱导组的梗死面积相似（p=0.79）；但与假手术对照相比，MI对照组的LVW/HW和HW/BW显著更大（所有比较p<0.01），而这些变化在MI-奈必洛尔组中无统计学意义。奈必洛尔还可防止血浆NO和ONOO-水平升高。
奈必洛尔治疗可减轻大鼠MI后的VR作用。这些有益作用与其降低心率和血压的作用无关。该化合物的一氧化氮调节作用可能有助于其对MI后发生的VR产生这些有益作用。
