Barsotti A, Dini F L, Nardini V, Di Muzio M, Gallina S, Di Napoli P, Calafiore A M, Trevi G
Istituto di Clinica Cardiovascolare, Università degli Studi G D'Annunzio, Chieti.
Cardiologia. 1993 Dec;38(12 Suppl 1):67-77.
In the progression from myocardial hypertrophy to heart failure, abnormalities in the interstitial space of the heart seem to play a critical role. The formation of an extracellular oedema and the alterations in coronary subendocardial perfusion are associated with the development of interstitial fibrosis. Cardiac experimental studies documented the presence of augmented interstitial fluid volume and pressure and a subsequent remodelling of the fibrillar network of the extracellular space of the myocardium during the phases of the cardiovascular response to a sudden overload. Variations of the Starling's forces balance caused by enhanced endothelial permeability or due to an impairment of cardiac lymphatic drainage may contribute to the development of an acute heart failure. During stable hyperfunction, the organization of a chronic oedema should account for interstitial changes in the hypertrophic myocardium. Reactive fibrosis seems to be under hormonal control. The activation of the renin-angiotensin-aldosterone system is responsible for interfascicular and intercellular accumulation of fibrillar collagen within the cardiac interstitium. Perivascular fibrosis in the subendocardium may impair intramyocardial distribution of coronary flow. When an inadequate hypertrophy occurs, because of an elevation in ventricular wall stress, myocardial oxygen consumption rises and this may lead to the exhaustion of coronary blood flow reserve in the subendocardial layers. This underperfusion may be responsible for the development of myocardial ischemia. Coronary hemodynamic changes in the microcirculation as those prompted by interstitial alterations may contribute to the onset of myocyte necrosis and to the formation of restorative fibrosis. The progressive mechanical overload of the spared hypertrophied myocytes could explain the initiation of a positive feedback mechanism which perpetuates endomyocardial perfusion impairment, interstitial oedema and remodelling, finally, causing myocyte deaths and fibrous tissue proliferation. These structural alterations and their pathophysiological counterparts appear to be closely related to the evolution from compensatory hypertrophy to chronic myocardial failure in hypertrophic heart disease.
在从心肌肥厚发展到心力衰竭的过程中，心脏间质空间的异常似乎起着关键作用。细胞外水肿的形成以及冠状动脉心内膜下灌注的改变与间质纤维化的发展有关。心脏实验研究表明，在心血管对突然过载的反应阶段，心肌间质液体积和压力增加，随后心肌细胞外空间的纤维网络发生重塑。内皮通透性增强或心脏淋巴引流受损导致的Starling力平衡变化可能促成急性心力衰竭的发生。在稳定的高功能状态下，慢性水肿的形成应归因于肥厚心肌的间质变化。反应性纤维化似乎受激素控制。肾素-血管紧张素-醛固酮系统的激活导致心脏间质内束间和细胞间纤维状胶原的积聚。心内膜下的血管周围纤维化可能损害心肌内冠状动脉血流的分布。当发生不适当的肥厚时，由于心室壁应力升高，心肌耗氧量增加，这可能导致心内膜下层冠状动脉血流储备耗尽。这种灌注不足可能是心肌缺血发生的原因。间质改变引发的微循环中的冠状动脉血流动力学变化可能促成心肌细胞坏死的发生和修复性纤维化的形成。剩余肥厚心肌细胞的渐进性机械过载可以解释正反馈机制的启动，该机制使心内膜灌注损害、间质水肿和重塑持续存在，最终导致心肌细胞死亡和纤维组织增生。这些结构改变及其病理生理对应物似乎与肥厚性心脏病中从代偿性肥厚到慢性心肌衰竭的演变密切相关。
