Mechanisms and models in heart failure - A combinatorial approach
Mechanisms and models in heart failure - A combinatorial approach
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DOI：
10.1161/01.cir.100.9.999
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发表时间：
1999-08-31
期刊：
影响因子：
37.8
通讯作者：
Mann, DL
中科院分区：
文献类型：
--
作者：
Mann, DL
几天到几个月到几年的时间。已经描述的代偿机制的组合包括交感神经系统和盐和水保持系统的早期激活，以保持心输出量，6-8以及血管舒张分子家族的激活，包括利钠肽、前列腺素（PGE 2和PGEI 2）和一氧化氮。然而，值得强调的是，我们对可能参与这一过程的分子家族的理解还远远没有完成。此外，我们对遗传背景、性别、年龄或环境如何影响这些补偿机制的信息很少。如图1所示，在心脏的泵送能力的初始下降之后激活的代偿机制能够在生理/稳态范围内调节LV功能，使得患者的功能能力被保留或仅被最小程度地抑制。因此，患者可能在数年内保持无症状或轻微症状。然而，在某个时间点，患者将变得明显的症状，从而导致发病率和死亡率的显著增加。为什么会发生这种向症状性心力衰竭的转变，以及这种转变究竟是如何发生的，以及它是否发生在所有LV功能障碍患者中仍然未知，这代表了心力衰竭的一个重要发现领域。然而，众所周知，向症状性心力衰竭的转变伴随着神经激素和细胞因子系统的进一步激活，以及心肌内的一系列适应性变化，统称为LV重塑。尽管在向症状性心力衰竭转变期间心脏的总体泵送能力进一步适度下降，但实验和临床证据的权重表明心力衰竭进展的发生与患者的血流动力学状态无关。因此，很难将向症状性心力衰竭的转变单独归因于LV功能恶化。因此，从上述讨论中产生的一个重要问题是为什么心力衰竭进展。
for a period of days to months to years. The portfolio of compensatory mechanisms that have been described include early activation of the sympathetic nervous system and salt and water retaining systems in order to preserve cardiac output, 6–8 as well as activation of a family of vasodilatory molecules, including natriuretic peptides, prostaglandins (PGE2 and PGEI2) and nitric oxide. 9, 10 However, it bears emphasis that our understanding of the family of molecules that may be involved in this process is far from complete. Moreover, we have very little information with respect to how genetic background, gender, age, or environment impact these compensatory mechanisms. As shown in Figure 1, the compensatory mechanisms activated following the initial decline in the pumping capacity of the heart are able to modulate LV function within a physiological/homeostatic range, such that the functional capacity of the patient is preserved or is depressed only minimally. Thus, patients may remain asymptomatic or minimally symptomatic for a period of years. However, at some point in time patients will become overtly symptomatic, with a resultant striking increase in morbidity and mortality. Why this transition to symptomatic heart failure occurs, and exactly how this transition occurs, and whether it occurs in all patients with LV dysfunction remains unknown and represents an important area of discovery in heart failure. What is known, however, is that the transition to symptomatic heart failure is accompanied by further activation of neurohormonal and cytokine systems, as well as a series of adaptive changes within the myocardium, collectively referred to as LV remodeling. Although there are further modest declines in the overall pumping capacity of the heart during the transition to symptomatic heart failure, the weight of experimental and clinical evidence suggests that heart failure progressions occur independently of the hemodynamic status of the patient. Accordingly, it becomes difficult to ascribe the transition to symptomatic heart failure to worsening LV function alone. Thus, one important question that arises from the above discussion is why heart failure progresses.