Department of Cardiothoracic Surgery, Stanford University, Falk Cardiovascular Research Building CV-235, 300 Pasteur Drive, Stanford, CA, 94305-5407, USA.
Department of Mechanical Engineering, Stanford University, Stanford, CA, USA.
Cardiovasc Eng Technol. 2023 Feb;14(1):129-140. doi: 10.1007/s13239-022-00641-3. Epub 2022 Aug 8.
Rheumatic heart disease is a major cause of mitral valve (MV) dysfunction, particularly in disadvantaged areas and developing countries. There lacks a critical understanding of the disease biomechanics, and as such, the purpose of this study was to generate the first ex vivo porcine model of rheumatic MV disease by simulating the human pathophysiology and hemodynamics.
Healthy porcine valves were altered with heat treatment, commissural suturing, and cyanoacrylate tissue coating, all of which approximate the pathology of leaflet stiffening and thickening as well as commissural fusion. Hemodynamic data, echocardiography, and high-speed videography were collected in a paired manner for control and model valves (n = 4) in an ex vivo left heart simulator. Valve leaflets were characterized in an Instron tensile testing machine to understand the mechanical changes of the model (n = 18).
The model showed significant differences indicative of rheumatic disease: increased regurgitant fractions (p < 0.001), reduced effective orifice areas (p < 0.001), augmented transmitral mean gradients (p < 0.001), and increased leaflet stiffness (p = 0.025).
This work represents the creation of the first ex vivo model of rheumatic MV disease, bearing close similarity to the human pathophysiology and hemodynamics, and it will be used to extensively study both established and new treatment techniques, benefitting the millions of affected victims.
风湿性心脏病是二尖瓣(MV)功能障碍的主要原因,特别是在贫困地区和发展中国家。目前对该疾病的生物力学缺乏深入的了解,因此,本研究旨在通过模拟人类病理生理学和血液动力学,首次建立风湿性 MV 疾病的离体猪模型。
采用热疗、缝合、氰基丙烯酸酯组织涂层等方法改变健康猪瓣膜,这些方法均近似模拟了瓣叶僵硬和增厚以及交界融合的病理过程。在离体左心模拟器中,对对照和模型瓣膜(n=4)进行了配对的血流动力学数据、超声心动图和高速录像采集。在 Instron 拉伸试验机中对瓣膜小叶进行力学特性测试,以了解模型的机械变化(n=18)。
模型显示出明显的风湿性疾病特征:反流分数增加(p<0.001),有效瓣口面积减小(p<0.001),跨瓣平均梯度增加(p<0.001),瓣叶僵硬度增加(p=0.025)。
本研究首次建立了风湿性 MV 疾病的离体模型,与人类病理生理学和血液动力学非常相似,该模型将被用于广泛研究已确立和新的治疗技术,使数百万受影响的患者受益。