Effects of aortic compliance and Windkessel reduction on cardiac and aortic pathophysiology

项目总结 主动脉弹性会产生温克塞尔效应。也就是说，动脉在血液从左侧射出后扩张。 收缩时的左心室，然后在主动脉瓣关闭后回缩。脑室动脉的这一特点 联合钝化峰值血压和血流波提供缓冲作用，保护心脏免受 压伤。此外，温克塞尔效应有助于血液远端通过冠状动脉和 心脏松弛时的外周运动。主动脉支架移植物是由坚硬的材料制成的，这种材料可以使主动脉变得僵硬。 并减弱温克塞尔效应。这可能会使心脏过度劳累，最终导致病理变化。 虽然僵硬的支架移植物通常被认为在主动脉中工作良好，但与之相关的微妙的长期影响 支架移植在主要关注死亡率和局部病变的支架移植文献中可能没有报道。 并发症需要再次干预。我们团队的最新证据表明，植入僵尸 年轻创伤患者接受胸主动脉支架植入术后左室壁和重量显著增加 在猪身上，会导致主动脉僵硬和早期左室纤维化。最近也有类似结果的报道。 胸腹主动脉支架植入术的老年患者。为了减轻这些影响， 为了保持主动脉顺应性，我们的团队开发了一种新的弹性纳米纤维主动脉支架，它可以 具有类似于主动脉的机械性能和微观结构，并能够保持主动脉的弹性和 温克塞尔效应，并保持正常的压力波形，而不是僵硬的传统支架 体外培养。此外，在体内，我们的纳米纤维材料保持其顺应性，经历快速 内皮化，并迅速融入动脉壁。我们建议检验这个假设 使用新一代顺应性支架-移植物保护主动脉顺应性 血液动力学和预防心脏和主动脉病变。这一假设将在3个月内得到检验 明确的目标。在目标1中，我们将制造具有可调顺应性的纳米纤维弹性支架移植物。在……里面 目的2我们将量化支架-移植物顺应性对人和猪主动脉温克塞尔功能的影响。 使用体外流动模型。最后，在目标3中，我们将评估支架-移植物顺应性对患者的体内影响 猪模型的血流动力学及心脏和主动脉病理。这将通过比较 商业用药时主动脉顺应性和温克塞尔减容对心脏和主动脉的影响 支架移植物与使用硬质和顺应性纳米纤维材料制成的装置。这个项目将量化 刚性支架对主动脉顺应性和心脏病理生理的影响，并将提出一种新的- 新一代支架移植物，保护主动脉和心脏免受病理重塑的影响。虽然合规性是 在年轻的大动脉中最高，心脏较弱的老年患者可能对其变化最敏感。考虑 硬性支架在所有年龄段患者中的普遍使用，更好的微创治疗的临床重要性 主动脉装置很难被高估。

PROJECT SUMMARY Aortic elasticity creates a Windkessel effect. That is, aortas distend following ejection of blood from the left ventricle (LV) during systole, and then recoil after aortic valve closure. This feature of ventricular-arterial coupling blunts peak blood pressure and flow waves providing a cushioning effect that protects the heart from pressure injury. In addition, the Windkessel effect helps move blood distally through the coronary arteries and periphery during cardiac relaxation. Aortic stent-grafts are made of stiff materials that artificially stiffen the aorta and diminish the Windkessel effect. This may overwork the heart, eventually leading to pathological changes. While stiff stent-grafts are generally thought to work well in the aorta, the subtle long-term effects associated with stent-grafting may not be reported in the stent-graft literature that focuses primarily on mortality and local complications requiring re-intervention. Recent evidence from our team demonstrates that implantation of stiff thoracic aortic stent-grafts in young trauma patients is associated with significantly increased LV mass and wall thickness, and in pigs results in aortic stiffening and early LV fibrosis. Similar outcomes were recently reported in elderly patients with thoracic and abdominal aortic stent-grafts. In order to mitigate these effects and preserve aortic compliance, our team has developed a new elastomeric nanofibrillar aortic stent-graft that possesses aorta-like mechanical properties and microstructure, and is able to preserve aortic elasticity and the Windkessel effect, and maintain normal pressure waveforms as opposed to stiff conventional stent-grafts in vitro. Furthermore, in vivo our nanofibrillar material maintains its compliance, undergoes rapid endothelialization, and gets quickly incorporated into the arterial wall. We propose to test the hypothesis that preservation of aortic compliance with a new-generation compliant stent-graft results in normal hemodynamics and prevents cardiac and aortic pathologies. This hypothesis will be tested through 3 Specific Aims. In Aim 1 we will manufacture nanofibrillar elastomeric stent-grafts with tunable compliance. In Aim 2 we will quantify the effect of stent-graft compliance on Windkessel function in human and porcine aortas using an ex vivo flow model. Finally, in Aim 3 we will assess the in vivo effects of stent-graft compliance on hemodynamics and cardiac and aortic pathologies in a swine model. This will be done by comparing the effects of aortic compliance and Windkessel reduction on the heart and the aorta when using commercial stent-grafts versus devices made using stiff and compliant nanofibrillar materials. This project will quantify the effects of stiff stent-grafts on aortic compliance and cardiac pathophysiology, and will propose a new- generation stent-graft that protects the aorta and the heart from pathologic remodeling. While compliance is highest in young aortas, older patients with weaker hearts may be most sensitive to its alteration. Considering the ubiquitous use of stiff stent-grafts in patients of all ages, the clinical importance of better minimally-invasive aortic devices is difficult to overestimate.