EXERCISE TRAINING IN POSTINFARCT HEART

描述：存活的心室的收缩功能 心肌梗死(MI)通过运动训练得到改善。海流 提案的重点是运动训练效果的细胞机制 收缩功能的改善。我们的数据显示两者都被更改了 运动训练和心肌梗死细胞内(Ca~(2+))i动态变化对钙离子浓度的影响 正常心肌细胞的内流和外流途径。我们假设那次演习 训练可以：(I)恢复正常的(钙)i动力学和收缩功能 对心肌梗死细胞的作用；以及(Ii)逆转心肌梗死后亚细胞内钙离子的病理变化 调控途径。为了验证我们的假设，雄性SD大鼠将 接受左室梗死，允许恢复3周，与Echo研究 匹配左室梗死面积(35%-50%)，然后开始6周高位 高强度短跑训练(HIST)。隔膜单个肌细胞(远程 来自疤痕)和LV游离壁(接近疤痕)将被隔离 久坐(SED，MISD)和运动训练(HIST，MIHIST)大鼠。(Ca2+)i 动力学、收缩功能与肌球蛋白重链亚型分布 将用显微荧光法、视频边缘检测器同时测量 和单细胞SDS-PAGE。钙离子通过L型钙离子通道和钠-钙离子通道内流 用全细胞膜片钳测量细胞交换量。可释放的肌质网钙离子 含量将用咖啡因诱导的SR钙释放和快速 凉爽的痉挛。将检查SR钙离子摄取和SR钙离子泄漏。 最后，将进行钙离子通量的操作以测试 认为(钙)i动力学改变与抑郁有因果关系的假说 心肌梗死细胞收缩功能及HIST对心肌细胞收缩功能的影响 心肌细胞收缩是通过调节钙离子稳态来实现的 小路。

DESCRIPTION: Contractile function in ventricles surviving substantial myocardial infarction (MI) is improved by exercise training. The current proposal focuses on cellular mechanisms by which exercise training effects an improvement in contractile function. Our data demonstrate both altered (Ca2+)i dynamics in MI myocytes and exercise training enhance both Ca2+ influx and efflux pathways in normal myocytes. We hypothesize that exercise training can: (i) restore normal (Ca2+)i dynamics and contractile function to MI myocytes; and (ii) reverse MI-induced pathology in subcellular Ca2+ regulatory pathways. To test our hypothesis, male Sprague-Dawley rats will undergo LV infarct, allowed to recover for 3 weeks, studied with Echo to match LV infarct size (35-50 percent), and then start a 6-week high intensity sprint training (HIST). Single myocytes from the septum (remote from scar) and LV free wall (close to the scar) will be isolated from sedentary (Sed, MISed) and exercised-trained (HIST, MIHIST) rats. (Ca2+)i dynamics, contractile function and myosin heavy chain isoform distribution will be simultaneously measured with microfluorimetry, video edge detector and single cell SDS-PAGE. Ca2+ influx via L-type Ca2+ channel and Na+-Ca2+ exchange will be measured with whole-cell patch clamp. Releasable SR Ca2+ content will be assayed with caffeine induced SR Ca2+ release and rapid cooling contractures. SR Ca2+ uptake and SR Ca2+ leak will be examined. Finally, manipulations of Ca2+ fluxes will be undertaken to test the hypothesis that altered (Ca2+)i dynamics is causally related to depressed contraction function in MI myocytes and that HIST's beneficial effects on myocyte contractions are mediated via modulation of Ca2+ homeostatic pathways.