Synergistic exacerbation of diastolic stiffness from short-term tachycardia-induced cardiodepression and angiotensin II.
Synergistic exacerbation of diastolic stiffness from short-term tachycardia-induced cardiodepression and angiotensin II.
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短期心动过速引起的心脏抑制和血管紧张素 II 协同加剧舒张期僵硬度。
DOI：
10.1161/01.res.82.4.503
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发表时间：
1998
影响因子：
20.1
通讯作者：
Kass,DA
中科院分区：
文献类型：
--
作者：
Senzaki,H;Gluzband,YA;Pak,PH;Crow,MT;Janicki,JS;Kass,DA
- 血管紧张素II（Ang II）和不断发展的心脏抑制之间的协同相互作用可能在恶化的心腔功能中发挥重要作用，特别是在胆固醇中。为了验证这一假设，18只清醒的狗在48小时快速起搏诱导亚急性心脏抑制前4天和诱导过程中以10或17 ng · kg-1· min-1输注Ang II。较低剂量产生的全身压力变化可忽略不计。另外12只动物作为仅起搏对照。记录压力-尺寸关系，并获得一系列内膜活检，以评估组织学和金属蛋白酶（MMP）的变化。单独48小时起搏可降低收缩功能，但对舒张僵硬度影响不大。单独的Ang II在两种剂量下仅适度提高舒张刚度，并在较高剂量下增强收缩力。输注7天后，这些变化恢复至基线水平。然而，Ang II（两种剂量）联合48小时起搏显著增加心室僵硬度（基线值的110±26%）和舒张末期压（22±1.7 mm Hg）。与此相反，起搏诱导的正性肌力和舒张异常并没有加剧血管紧张素II。酶谱显示MMP激活（72-和92-kD明胶酶和52-kDa酪蛋白酶）后，4天的血管紧张素II输注（在两个剂量），持续起搏。停止7天Ang II输注后24小时开始的快速起搏也导致舒张硬化，并与MMP重新激活相对应。血管紧张素II也诱导心肌细胞坏死，炎症，随后间质纤维化，但这些变化与腔力学。因此，血管紧张素II放大和加速舒张功能障碍时，结合不断发展的心脏抑制。当心室扩张性下降时，这种现象也可能是晚期心肌病中Ang II影响的基础。
—Synergistic interaction between angiotensin II (Ang II) and evolving cardiodepression may play an important role in worsening chamber function, particularly in diastole. To test this hypothesis, Ang II was infused at 10 or 17 ng · kg−1· min−1in 18 conscious dogs 4 days before and during induction of subacute cardiodepression by 48-hour tachypacing. The lower dose yielded negligible systemic pressure changes. Twelve additional animals served as paced-only controls. Pressure-dimension relations were recorded, and serial endocardial biopsies were obtained to assess histological and metalloproteinase (MMP) changes. Forty-eight–hour pacing alone depressed systolic function but had little effect on diastolic stiffness. Ang II alone only modestly raised diastolic stiffness at both doses and enhanced contractility at the higher dose. These changes recovered toward baseline after a 7-day infusion. However, Ang II (at either dose) combined with 48-hour pacing markedly increased ventricular stiffness (110±26% over baseline) and end-diastolic pressure (22±1.7 mm Hg). In contrast, pacing-induced inotropic and relaxation abnormalities were not exacerbated by Ang II. Zymography revealed MMP activation (72- and 92-kD gelatinases and 52-kDa caseinase) after a 4-day Ang II infusion (at both doses), which persisted during pacing. Tachypacing initiated 24 hours after cessation of a 7-day Ang II infusion also resulted in diastolic stiffening and corresponded with MMP reactivation. Ang II also induced myocyte necrosis, inflammation, and subsequent interstitial fibrosis, but these changes correlated less with chamber mechanics. Thus, Ang II amplifies and accelerates diastolic dysfunction when combined with evolving cardiodepression. This phenomenon may also underlie Ang II influences in late-stage cardiomyopathy, when chamber distensibility declines.