Novel rat model of ischemic cardiomyopathy induced by repetitive myocardial ischemia/reperfusion injury while conscious
Novel rat model of ischemic cardiomyopathy induced by repetitive myocardial ischemia/reperfusion injury while conscious
复制标题
DOI：
10.1253/circj.71.788
复制
发表时间：
2007-05-01
影响因子：
3.3
通讯作者：
Yoshida, Kiyoshi
中科院分区：
文献类型：
--
作者：
Toyota, Eiji;Kawaguchi, Yukie;Yoshida, Kiyoshi
背景清醒状态下反复短暂缺血再灌注(I/R)所致大鼠缺血性心肌病(ICM)动物模型尚未建立。在清醒状态下采用重复的I/R方案(20只S，2min，然后主缺血30min，每48h一次，持续4周)。I/R方案不能诱导跨壁瘢痕的形成，但可导致(1)残留心肌细胞弥漫性纤维化(Masson trichrome染色)，(2)冠状动脉低灌注(201TI-Cl放射自显影)，(3)冠状动脉微血管体积分数(MicroCT)降低，(4)逐渐进行性左心室(LV)扩张(超声心动图)。但3天时左室舒张面积增加的百分比与4周时左室扩张(r=0.77，p=0.0001)、纤维化(r=0.77，p=0.0034)、微血管减少(r=0.67，p=0.040)显著相关。意识状态下反复I/R诱导的ICM模型在晚期ICM的严重程度存在个体间差异，但在重复I/R初期，这种变化是非侵入性的(通过LV舒张性反应)。
Background A rodent model of ischemic cardiomyopathy (ICM) induced by repetitive brief ischemia/reperfusion (I/R) injury while conscious has not been previously established.Methods and Results A newly developed coronary occluder was implanted in male Wistar rats. A repetitive I/R protocol (20 s, 2 min, followed by main 30 min -ischemia, every 48 h, for 4 weeks) was introduced while the animals were conscious. The I/R protocol did not induce transmural scar formation but induced (1) residual myocytes with scattered infiltration of fibrosis (Masson trichrome stain), (2) coronary hypoperfusion (201TI-Cl autoradiogram), (3) reduced coronary microvascular volume fraction (microCT), and (4) gradually progressive left ventricular (LV) dilation (echocardiography). These parameters of ICM showed interindividual variation; however, the percent increase in LV diastolic area on day 3 was significantly correlated with LV dilation (r=0.91, p < 0.0001), fibrosis (r=0.77, p=0.0034), and reduction in microvessels (r=0.67, p=0.040) at week 4. The LV dilatory response on day 3 also correlated with inducible nitric oxide synthase expression (immunohistochemistry, day 3) in the LV (r=0.92, p=0.028).Conclusions A novel rat. model of ICM induced by repetitive I/R while conscious showed interindividual variation in the severity of ICM in the advanced stage, but this was predictable non-invasively (by LV dilatory response) during the initial stage of repetitive I/R.