Schipke Kimberly J, To S D Filip, Warnock James N
Department of Agricultural and Biological Engineering, Mississippi State University, MS, USA.
J Vis Exp. 2011 Aug 23(54):3316. doi: 10.3791/3316.
The aortic valve, located between the left ventricle and the aorta, allows for unidirectional blood flow, preventing backflow into the ventricle. Aortic valve leaflets are composed of interstitial cells suspended within an extracellular matrix (ECM) and are lined with an endothelial cell monolayer. The valve withstands a harsh, dynamic environment and is constantly exposed to shear, flexion, tension, and compression. Research has shown calcific lesions in diseased valves occur in areas of high mechanical stress as a result of endothelial disruption or interstitial matrix damage(1-3). Hence, it is not surprising that epidemiological studies have shown high blood pressure to be a leading risk factor in the onset of aortic valve disease(4). The only treatment option currently available for valve disease is surgical replacement of the diseased valve with a bioprosthetic or mechanical valve(5). Improved understanding of valve biology in response to physical stresses would help elucidate the mechanisms of valve pathogenesis. In turn, this could help in the development of non-invasive therapies such as pharmaceutical intervention or prevention. Several bioreactors have been previously developed to study the mechanobiology of native or engineered heart valves(6-9). Pulsatile bioreactors have also been developed to study a range of tissues including cartilage(10), bone(11) and bladder(12). The aim of this work was to develop a cyclic pressure system that could be used to elucidate the biological response of aortic valve leaflets to increased pressure loads. The system consisted of an acrylic chamber in which to place samples and produce cyclic pressure, viton diaphragm solenoid valves to control the timing of the pressure cycle, and a computer to control electrical devices. The pressure was monitored using a pressure transducer, and the signal was conditioned using a load cell conditioner. A LabVIEW program regulated the pressure using an analog device to pump compressed air into the system at the appropriate rate. The system mimicked the dynamic transvalvular pressure levels associated with the aortic valve; a saw tooth wave produced a gradual increase in pressure, typical of the transvalvular pressure gradient that is present across the valve during diastole, followed by a sharp pressure drop depicting valve opening in systole. The LabVIEW program allowed users to control the magnitude and frequency of cyclic pressure. The system was able to subject tissue samples to physiological and pathological pressure conditions. This device can be used to increase our understanding of how heart valves respond to changes in the local mechanical environment.
主动脉瓣位于左心室和主动脉之间，可实现血液单向流动，防止血液回流至心室。主动脉瓣小叶由悬浮于细胞外基质（ECM）中的间质细胞组成，并内衬有一层内皮细胞。该瓣膜承受着恶劣的动态环境，不断受到剪切力、弯曲力、张力和压力的作用。研究表明，由于内皮细胞破坏或间质基质损伤，病变瓣膜中的钙化病变发生在机械应力较高的区域（1 - 3）。因此，流行病学研究表明高血压是主动脉瓣疾病发病的主要危险因素也就不足为奇了（4）。目前针对瓣膜疾病唯一可用的治疗选择是用生物假体或机械瓣膜手术置换病变瓣膜（5）。更好地理解瓣膜生物学对物理应力的反应将有助于阐明瓣膜发病机制。反过来，这有助于开发非侵入性疗法，如药物干预或预防。此前已经开发了几种生物反应器来研究天然或工程心脏瓣膜的力学生物学（6 - 9）。脉动生物反应器也已被开发用于研究包括软骨（10）、骨骼（11）和膀胱（12）在内的一系列组织。这项工作的目的是开发一种循环压力系统，可用于阐明主动脉瓣小叶对压力负荷增加的生物学反应。该系统由一个丙烯酸腔室组成，用于放置样本并产生循环压力；氟橡胶隔膜电磁阀用于控制压力循环的时间；还有一台计算机用于控制电气设备。使用压力传感器监测压力，并使用称重传感器调节器调节信号。LabVIEW程序通过模拟设备以适当速率将压缩空气泵入系统来调节压力。该系统模拟了与主动脉瓣相关的动态跨瓣膜压力水平；锯齿波产生压力的逐渐增加，这是舒张期瓣膜上存在的典型跨瓣膜压力梯度，随后是描绘收缩期瓣膜开放的急剧压力下降。LabVIEW程序允许用户控制循环压力的大小和频率。该系统能够使组织样本承受生理和病理压力条件。此设备可用于增进我们对心脏瓣膜如何响应局部机械环境变化的理解。
