Salloum Fadi N, Chau Vinh Q, Hoke Nicholas N, Kukreja Rakesh C
Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Room 7-020A, Richmond, VA, 23298-0204, USA,
Cardiovasc Drugs Ther. 2014 Dec;28(6):493-500. doi: 10.1007/s10557-014-6559-0.
Phosphodiesterase-5 (PDE5) inhibitors were shown to exert powerful protection in various animal models of cardiomyopathy. Tadalafil is a long-acting and highly specific PDE5 inhibitor, which makes it the most attractive in its class for long-term management of patients with heart failure. We studied the effects of tadalafil in attenuating ischemic cardiomyopathy in mice.
Adult male mice underwent myocardial infarction (MI) by permanent left coronary artery ligation and were treated daily with tadalafil (1 mg/kg; ip) or volume-matched 10% DMSO for 4 weeks. Twenty four hours after coronary ligation, infarct size, measured by TTC staining, was reduced from 70.1 ± 3.1% in DMSO-treated group to 49.3 ± 2.6% with tadalafil (P < 0.05). Similarly, tadalafil treatment yielded a smaller fibrotic area (8.8 ± 2.8% of LV), assessed by Masson's trichrome staining, as compared to DMSO group (21.9 ± 3.9%, P < 0.05). Apoptosis, measured by TUNEL assay, also declined with tadalafil (2.1 ± 0.2%) as compared to DMSO (6.7 ± 0.4%, P < 0.05) at 28 days post MI. Tadalafil also attenuated the increase in cardiac hypertrophy and pulmonary edema following infarction. These parameters reflect diminished left ventricular (LV) adverse remodeling and preserved fractional shortening with tadalafil at 7 and 28 days post infarction.
Tadalafil attenuates ischemic cardiomyopathy in mice and preserves LV function.
磷酸二酯酶-5（PDE5）抑制剂已被证明在各种心肌病动物模型中具有强大的保护作用。他达拉非是一种长效且高度特异性的PDE5抑制剂，这使其成为该类药物中对心力衰竭患者进行长期管理最具吸引力的药物。我们研究了他达拉非对减轻小鼠缺血性心肌病的作用。
成年雄性小鼠通过永久性左冠状动脉结扎术诱导心肌梗死（MI），并每天接受他达拉非（1 mg/kg；腹腔注射）或体积匹配的10%二甲基亚砜（DMSO）治疗4周。冠状动脉结扎24小时后，通过TTC染色测量的梗死面积，在DMSO治疗组中为70.1±3.1%，而他达拉非治疗组为49.3±2.6%（P<0.05）。同样，与DMSO组（21.9±3.9%，P<0.05）相比，通过Masson三色染色评估，他达拉非治疗产生的纤维化面积更小（左心室的8.8±2.8%）。通过TUNEL检测测量的凋亡，在心肌梗死后28天时，他达拉非组（2.1±0.2%）也比DMSO组（6.7±0.4%，P<0.05）有所下降。他达拉非还减轻了梗死后心脏肥大和肺水肿的增加。这些参数反映了梗死7天和28天时，他达拉非组左心室（LV）不良重塑减少，射血分数保留。
他达拉非可减轻小鼠缺血性心肌病并保留左心室功能。
