Early exercise training normalizes myofilament function and attenuates left ventricular pump dysfunction in mice with a large myocardial infarction
Early exercise training normalizes myofilament function and attenuates left ventricular pump dysfunction in mice with a large myocardial infarction
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DOI：
10.1161/01.res.0000262655.16373.37
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发表时间：
2007-04-13
影响因子：
20.1
通讯作者：
Duncker, Dirk J.
中科院分区：
文献类型：
--
作者：
de Waard, Monique C.;van der Velden, Jolanda;Duncker, Dirk J.
心肌梗死（MI）后早期运动训练对心脏益处的程度和机制尚不完全清楚，但可能涉及Ca2+处理和肌丝功能异常的钝化。因此，我们研究了大心肌梗死后早期开始的8周自愿运动对小鼠左心室重塑和功能障碍的影响。运动对生存率、心肌梗死大小或左室尺寸均无影响，但可使左室分数缩短从8 +/- 1%提高到12 +/- 1%，LVdP/dt（P30）从5295 +/- 207降至5794 +/- 207 mmhg /s (P均< 0.05)，并减少肺充血。这些运动的整体影响与心肌梗死引起的肌丝Ca2+敏感性增加的正常化有关（δ pCa(50) = 0.037）。运动的这种效果是pka介导的，可能是因为β(1)-肾上腺素能信号的改善，β（1)-肾上腺素能受体蛋白（48%）和cAMP水平（36%）增加，均P < 0.05）。运动阻止了mi诱导的剥皮心肌细胞最大发力能力的下降（F-max从14.3 +/- 0.7增加到18.3 +/- 0.8 kN/m） (2) P < 0.05)，这与未加载的完整心肌细胞缩短的增强有关（从4.1 +/- 0.3增加到7.0 +/- 0.6%,P < 0.05）。此外，尽管SERCA2a和PLB表达以及PLB磷酸化状态不变，但运动降低了舒张期Ca2+浓度（类似30%，P < 0.05）。重要的是，运动对Ca2+瞬态振幅没有影响，这表明LV的改善和心肌细胞的缩短主要是因为肌丝功能的改善。综上所述，小鼠重度心肌梗死后的早期运动对左室重塑没有影响，但会减轻整体左室功能障碍。后者可以通过运动诱导的肌丝功能改善来解释。
The extent and mechanism of the cardiac benefit of early exercise training following myocardial infarction (MI) is incompletely understood, but may involve blunting of abnormalities in Ca2+-handling and myofilament function. Consequently, we investigated the effects of 8-weeks of voluntary exercise, started early after a large MI, on left ventricular (LV) remodeling and dysfunction in the mouse. Exercise had no effect on survival, MI size or LV dimensions, but improved LV fractional shortening from 8 +/- 1 to 12 +/- 1%, and LVdP/dt(P30) from 5295 +/- 207 to 5794 +/- 207 mm Hg/s (both P < 0.05), and reduced pulmonary congestion. These global effects of exercise were associated with normalization of the MI-induced increase in myofilament Ca2+-sensitivity (Delta pCa(50) = 0.037). This effect of exercise was PKA-mediated and likely because of improved beta(1)-adrenergic signaling, as suggested by the increased beta(1)-adrenoceptor protein (48%) and cAMP levels (36%; all P < 0.05). Exercise prevented the MI-induced decreased maximum force generating capacity of skinned cardiomyocytes (F-max increased from 14.3 +/- 0.7 to 18.3 +/- 0.8 kN/m(2) P < 0.05), which was associated with enhanced shortening of unloaded intact cardiomyocytes (from 4.1 +/- 0.3 to 7.0 +/- 0.6%; P < 0.05). Furthermore, exercise reduced diastolic Ca2+-concentrations (by similar to 30%, P < 0.05) despite the unchanged SERCA2a and PLB expression and PLB phosphorylation status. Importantly, exercise had no effect on Ca2+-transient amplitude, indicating that the improved LV and cardiomyocyte shortening were principally because of improved myofilament function. In conclusion, early exercise in mice after a large MI has no effect on LV remodeling, but attenuates global LV dysfunction. The latter can be explained by the exercise-induced improvement of myofilament function.