Early predictors of cardiac decompensation in experimental volume overload
Early predictors of cardiac decompensation in experimental volume overload
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DOI：
10.1007/s11010-009-0361-5
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发表时间：
2010-05-01
影响因子：
4.3
通讯作者：
Deschepper, Christian F.
中科院分区：
文献类型：
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作者：
Oliver-Dussault, Christelle;Ascah, Alexis;Deschepper, Christian F.
在人类中，容量超负荷（VOL）增加了心脏性猝死的风险，但也存在重要的个体间变异性，可能是因为遗传背景的差异。尽管VOL对心肌特性有快速的影响，但尚不清楚这些早期反应的严重程度与持续VOL对死亡率的影响有多大程度的相关性。为了测试这个问题，我们在来自两个遗传不同品系的雄性大鼠中诱导VOL [即，Sprague-Dawley（SD）和Wistar Kyoto衍生的多动（WKHA）大鼠]通过建立外科腹膜腔瘘（ACF）。在ACF 39周后，只有36%的SD大鼠存活，而手术的WKHA大鼠存活率为82%。我们还监测了心肌血流动力学功能，线粒体特性，左心室（LV）形态和左心室壁舒张特性在不同的时间范围从2至12周后，无论是ACF或假手术。ACF对两种大鼠品系的LV壁都有快速影响，但在死亡倾向SD品系中受影响程度更大的唯一变量是标准化LV重量、LV腔面积和心肌壁硬度。相比之下，ACF影响血流动力学和线粒体功能的方式仅存在边缘应变相关差异。因此，虽然左心室壁对ACF的早期形态反应（沿着其对心肌舒张壁应力的下游影响）与晚期死亡率的应变依赖性差异相关良好，但其他功能变化显示无预测作用。因此，密切监测心脏几何结构的早期变化（以及分析心肌舒张期应变的新方法）可能有助于进一步改善容量超负荷心脏病患者的风险分层。
In humans, volume overload (VOL) increases the risk of sudden cardiac death, but there is also important inter-individual variability, presumably because of differences in genetic backgrounds. Although VOL has rapid effects on myocardial properties, it is not known to which extent the severity of these early responses correlate with the effect of sustained VOL on mortality. In order to test this question, we induced VOL in male rats from two genetically distinct strains [i.e., Sprague-Dawley (SD) and Wistar Kyoto-derived Hyperactive (WKHA) rats] by creating a surgical aorto-caval fistula (ACF). Only 36% of SD rats remained alive after 39 weeks of ACF, in contrast to 82% of the operated WKHA rats. We also monitored myocardial hemodynamic function, mitochondrial properties, left ventricular (LV) morphology and LV wall diastolic properties at different times ranging from 2 to 12 weeks after either ACF or sham surgery. ACF had a rapid impact on the LV walls of both rat strains, but the only variables that were affected to a greater extent in the mortality-prone SD strain were normalized LV weight, LV cavity area, and myocardial wall stiffness. In contrast, there were only marginal strain-related differences in the way ACF affected hemodynamic and mitochondrial functions. Thus, while early morphologic responses of LV walls to ACF (along with their downstream consequences on myocardial diastolic wall stress) correlated well with strain-dependent differences in late mortality, other functional changes showed no predictive effects. Close monitoring of early changes in cardiac geometry (as well as new methods to analyze myocardial diastolic strain) might, therefore, be helpful to further improve risk stratification in humans with volume overload cardiopathies.