心室辅助逆转心脏重构的血液动力学因素及其“部分辅助”策略的实验研究

The clinical application of ventricular assist device (VAD) induces a few in end stage heart failure patients, who are waiting for the heart transplantation, to recover their cardiac function gradually, and to be separated from the VAD support and even no longer needs the heart transplantation finally. In the event the cardiac remodeling of patients are reversed. At present, however, the main hemodynamic factors of cardiac remodeling reverse caused by VAD support is not very clear. In clinic it is also found that the full-support of VAD does not appear to contribute to heart failure function recovery. Especially for the patients with irreversible myocardial injury, the “partial-support” strategy more easily increases the occurrence of cardiac remodeling reverse. This project intends to utilize the animal experimental method for exploring the hemodynamic impacts of hemodynamic on cardiac remodeling reverse and better VAD support strategy. On the basis of CH-VAD implantation in vivo survival experiments, we implant the VAD to total-support and partial-support the animals with congestive heart failure, proceeding throughout the cardiac remodeling reverse. During the process of cardiac remodeling reverse induced by VAD support, we investigate these parameters such as the cardiac hemodynamics, cardiac structure, cardiac tissue and the marker of cardiac dysfunction index changes, to survey the main hemodynamic factors on cardiac remodeling reverse. Comparing the effects between full-support and partial-supporting on reverse cardiac remodeling, we would found the experimental evidence for partial-support strategy is more conducive to reverse cardiac remodeling. Ultimately, we hope this project would provide the useful experimental basis for further studies on pathological mechanism of the cardiac remodeling reverse and application of VAD.

心室辅助装置(VAD)的临床应用使一些等待心脏移植的终末期心衰患者心脏功能逐渐恢复，最终永久脱离辅助机械且不再需要心脏移植，即发生心脏重构逆转，但目前人们对VAD 辅助致心脏重构逆转的血液动力学因素尚未进行系统研究。临床应用中还发现VAD 的“全部辅助”似乎不利于衰竭心脏的功能恢复，尤其对于尚未发生不可逆心肌损伤的患者，“部分辅助”策略更有可能增加心脏重构逆转的发生。基于此本项目拟采用动物实验的方法，在CH-VAD 植入在体存活实验基础上，对心衰动物进行部分和全部VAD辅助，重现心衰动物的心脏重构逆转过程。通过观察VAD 辅助前、中、后心脏血液动力学、心脏结构、心肌组织学及心衰标记物等指标的变化，探讨VAD 辅助致心脏重构逆转的主要血液动力学因素，找到VAD”部分辅助“策略更有利于心脏重构逆转的实验证据，最终为进一步探索心脏重构逆转的病理学机制，为VAD 的临床应用提供科学的实验依据。

心室辅助装置(VAD)的临床应用使一些等待心脏移植的终末期心衰患者心脏功能逐渐恢复，最终永久脱离辅助机械且不再需要心脏移植，即发生心脏重构逆转，但目前人们对VAD 辅助致心脏重构逆转的主要血液动力学因素尚不十分清楚。本研究中，我们首先利用离断二尖瓣腱索的方式摸索出大动物充血性心衰模型的制作方法，然后对4例心衰动物进行部分和全部VAD辅助，通过观察VAD 辅助前后心衰动物的舒张末左心室内压力、容积、每搏输出量（SV），以及心房利尿钠肽( ANP)、脑利尿钠肽( BNP)心衰标记物的变化情况，实验结果显示：（1）VAD辅助可致衰竭心脏重构逆转；（2）VAD辅助时，动物的左心室压力和容积明显降低，推测VAD辅助致心脏重构逆转可能的血流动力学因素数是左室压力和流量卸载；（3）动物脱机后，心衰动物采用VAD的部分辅助策略时其心脏功能的恢复略优于全部辅助。以上研究结果为进一步探索心脏重构逆转的病理学机制，为VAD 的临床应用提供了一定的科学实验依据。