Ventricular Restraint Therapy for Heart Failure

描述（由申请人提供）：本提案的主要假设是，心室抑制治疗可降低经壁压力、舒张末期容积和心肌耗氧量，以促进扩张性衰竭心脏的反向重构。先前的动物和初步临床研究证明了心室抑制治疗的前景和可行性，但仍存在许多问题。我们的实验室开发了一种新的心室抑制装置，能够通过使用心外膜球囊定量地抑制心室。我们的第一个具体目标是测量整个心脏周期的跨壁压力和左心室容积，推导压力-容积关系，并使用定量心室约束计算正常绵羊心脏的压力-容积面积。这一目的将证明心室约束对正常心脏的心室力学和能量学的影响。我们还将研究心室抑制对心肌灌注的急性影响。我们的第二个目标是在扩张型心肌病的绵羊梗死后模型中进行相同的测量。我们将在为期3个月的纵向研究中进行一系列测量，以评估舒张末期容积、心室收缩力、心肌灌注以及心室约束动物与对照动物反向重构的证据。这些目标的成功完成将有助于更好地理解心室抑制对心室生理学的影响。

DESCRIPTION (provided by applicant): The major hypothesis of this proposal is that ventricular restraint therapy reduces transmural pressure, end-diastolic volume, and myocardial oxygen consumption to promote reverse remodeling in a dilated failing heart. Prior animal and initial clinical studies demonstrate the promise and feasibility of ventricular restraint therapy, however many questions remain. Our lab has developed a novel ventricular restraint device capable of quantitative ventricular restraint through the use of an epicardial balloon. Our first specific aim is to measure transmural pressure and left ventricular volume throughout the cardiac cycle, derive the pressure-volume relationship and calculate the pressure-volume area using quantitative ventricular restraint in a normal ovine heart. This aim will demonstrate the effect of ventricular restraint on ventricular mechanics and energetics in a normal heart. We will also examine the acute effect of ventricular restraint on myocardial perfusion. Our second aim is to perform these same measurements in an ovine post-infarcted model of dilated cardiomyopathy. We will perform serial measurements over a 3-month longitudinal study to evaluate end-diastolic volume, ventricle contractility, myocardial perfusion, and evidence of reverse remodeling in ventricular restraint versus control animals. Successful completion of these aims will, lead to a better understanding of the effect of ventricular restraint on ventricular physiology.