QUANTITATIVE MORPHOLOGY OF CARDIAC HYPERTROPHY

体外收缩功能障碍是心肌肥厚的结果，即 是由心肌压力超负荷引起的。这是不正常的 功能发生压力过载是否来自慢性进展性 或者是严重超载。相比之下，容量超负荷导致的肥厚 不会导致体外收缩功能障碍。在这种情况下 压力超负荷诱导的肥大，如果这一过程被逆转，那么 收缩功能恢复正常。我们已经研究了早期的 急性压力超负荷右室肥厚并发现 是脑室结缔组织成分的增加 心肌与肌细胞大小和肌膜外表面的变化 面积/细胞体积比。结缔组织的变化与 压力超负荷肥大可能直接导致心脏受损 通过改变弹性体的弹性性能来实现收缩性能 脑室。心肌细胞大小和形状的改变可能对 间接地通过改变收缩的基本控制系统 仪器。这项提案的具体目的是确定这些 结构效果或其他结构修改，可在此找到 病理生理模型与收缩功能受损有因果关系 功能，因此对最终的变化具有病因学意义 在这个模型中找到的。由于慢性渐进性压力超负荷模型 不会造成心肌损伤，与急性心肌损伤的组织相比 压力过载模型将确定所看到的变化是否是 急性压力超负荷引起的心肌损伤。然后是一个 压力超负荷性右室肥厚的比较 心肌对容量超负荷的肥大心肌会进行识别 那些与异常收缩相关的结构改变 功能和一般与肥大过程相关的那些。 这些变化是心肌收缩功能障碍所特有的 当肥大过程逆转时，应该会恢复正常。这 会在反转慢性渐进性压力超负荷时进行检查 模特。形态计量学超微结构研究用于比较和 对比不同血流动力学状态下的右室心肌 条件。这些研究与我们的长远目标有关，即 确定导致功能异常的心肌改变和 最终导致心力衰竭。

In vitro contractile dysfunction is a result of cardiac hypertrophy that is caused by a pressure overload of the ventricular myocardium. This abnormal function occurs whether the pressure overload is from a chronic progressive or an acute overload. In contrast volume overload induced hypertrophy does not result in in vitro contractile dysfunction. In the case of the pressure overload induced hypertrophy, if this process is reversed then the contractile function returns to normal. We have studied an early stage of acute pressure overload right ventricular hypertrophy and found that there is an increase in the connective tissue components of the ventricular myocardium and a change in myocyte size and external sarcolemma surface area/ cell volume ratio. The change in connective tissue associated with pressure overload hypertrophy could contribute directly to compromised contractile performance by altering the elastic properties of the ventricle. The change in myocyte size and shape could contribute indirectly by altering the basic control systems for the contractile apparatus. The SPECIFIC AIM of this proposal is to determine whether these structural effects or other structural modifications that are found in this pathophysiological model are causally related to the impaired contractile function and therefore have etiologic significance for the eventual changes found in this model. Since the chronic progressive pressure overload model does not cause myocardial injury a comparison to the tissue from the acute pressure overload model will determine if the changes seen are a result of the myocardial injury produced by acute pressure overload. Then a comparison of the pressure overload hypertrophied right ventricular myocardium to the volume overload hypertrophied myocardium will identify those structural alterations associated with the abnormal contractile function and those associated with the hypertrophy process in general. Those alterations unique to the myocardium with contractile dysfunction should return to normal when the hypertrophy process is reversed. This will be examined in the reversed chronic progressive pressure overload model. Morphometric ultrastructural studies are used to compare and contrast the right ventricular myocardium under these different hemodynamic conditions. These studies relate to our long-term objectives which are to determine myocardial alterations that result in abnormal function and ultimately heart failure.