CLINICAL APPLICATION OF END SYSTOLIC P-V RELATIONS

这项研究提案的长期目标是确定一个时间 慢性左心室容量超负荷的外科治疗 主动脉瓣关闭不全(AR)或二尖瓣关闭不全(MR) 恢复正常的LV大小和性能。LV体积的自然历史 超负荷遵循一个潜在的可识别的血流动力学过程 以代偿性左室肥厚为特征，其次为左室收缩 在没有心肌功能障碍的情况下，最后， 不可逆转的心肌功能障碍。临床上常用的、非 有创、有创和有创指标倾向于识别AR和MR晚期患者 在其血流动力学过程中不可逆性心肌功能不全时 占主导地位。相比之下，这个实验室的初步数据 有力地支持了这一假说，即左心室收缩功能不全的缺失 AR和MR患者的心肌功能障碍可以通过 同时应用最大时变弹性和心肌刚度 概念，在这种情况下的左心室收缩功能障碍是 不充分的左室肥厚和球状几何假设，以及 此时对左心室容量过载的手术将逆转这些不利因素 血流动力学过程，从而保存或恢复正常的左心室大小和 性能。因此，这项研究建议的具体目的是： 1)用来表征LV腔性能和心肌特性 正常人的时变弹性和心肌硬度概念 患者，并与AR或MR患者进行对比；2) 建立LV腔弹性异常的发生机制 3)建立AR患者亚群 或MR根据有无或正常的LV室壁弹性和 心肌性质；4)确定改变的程度和时间进程 在AR和MR手术后一年的左心室大小和表现， 5)评价手术对AR和MR的独立影响 左心室弹性和心肌特性。这项研究建议 因此，代表了复杂的血液动力学的独特组合 集成的方法专注于提供新数据来定义 无心肌梗死患者左心室收缩功能障碍的机制 AR和MR患者的功能障碍和手术保留时间 或恢复正常的LV大小和性能。

The long-term goal of this research proposal is to define a time for surgery in chronic left ventricular (LV) volume overload resulting from aortic regurgitation (AR) or mitral regurgitation (MR) to preserve or restore normal LV size and performance. The natural history of LV volume overload follows a potentially identifiable hemodynamic course characterized by compensated LV hypertrophy, followed by LV systolic dysfunction in the absence of myocardial dysfunction, and finally, irreversible myocardial dysfunction. The commonly employed clinical, non- invasive, and invasive indices tend to identify patient with AR and MR late in their hemodynamic course when irreversible myocardial dysfunction predominates. In contrast, the preliminary data from this laboratory strongly support the hypotheses that LV systolic dysfunction in the absence of myocardial dysfunction can be identified in patients with AR and MR by applying both the maximum time-varying elastance and myocardial stiffness concepts, that LV systolic dysfunction in this setting is the result of inadequate LV hypertrophy and assumption of spherical geometry, and that surgery for LV volume overload at this time will reverse these detrimental hemodynamic processes and, thereby, preserve or restore normal LV size and performance. Therefore, the specific aims of this research proposal are: 1) to characterize LV chamber performance and myocardial properties using the time-varying elastance and myocardial stiffness concepts in normal patients and contrast them with those in patients with AR or MR; 2) to establish mechanisms for abnormal LV chamber elastance in the presence of normal myocardial properties; 3) to establish subgroups of patients with AR or MR based upon the presence or absence or normal LV chamber elastance and myocardial properties; 4) to define the extent and time course of changes in LV size and performance during the year following surgery for AR and MR, and 5) to characterize the independent effects of surgery for AR and MR on LV chamber elastance and myocardial properties. This research proposal represents, therefore, a unique combination of sophisticated hemodynamic approaches that are integrated to focus on providing new data to define the mechanisms for LV systolic dysfunction in the absence of myocardial dysfunction and a time for surgery in patients with AR and MR to preserve or restore normal LV size and performance.