Jensen M O, Lemmon J D, Gessaghi V C, Conrad C P, Levine R A, Yoganathan A P
Georgia Institute of Technology/Emory School of Biomedical Engineering, Atlanta 30332-0535, USA.
J Heart Valve Dis. 2001 Jan;10(1):111-24.
Recent developments suggest that stentless bioprosthetic mitral valve heterografts should be considered in order to optimize valve hydrodynamics. The fixation process alters the mechanical properties of tissue. This study investigates the changes in mitral valve morphology and hemodynamic performance following fixation.
Porcine mitral valves were excised and attached to a physiological annular ring. Mitral valve function was studied in vitro with a rigid transparent left heart model, allowing transverse and sagittal views. Initial experiments were performed with fresh valves under physiological conditions. Three different papillary muscle positions were used, and each was recorded. After glutaraldehyde fixation, genipin fixation, and cryopreservation, the valves were re-studied while maintaining cardiac output. Performance characteristics before and after fixation were obtained from hydrodynamic pressure and flow data, high-speed video camera, digital video, Doppler ultrasound, and three-dimensional papillary muscle force measurements. Morphology changes were detected by detailed anatomic measurements of the valves before and after fixation.
Valve length was reduced by 18.5% after fixation with genipin (p <0.001), but not with glutaraldehyde. Cryopreserved valves showed no statistically significant changes in morphology or hydrodynamic performance after preservation. The forward flow opening area was reduced by 12.2% (p <0.001) after glutaraldehyde fixation, and by 32.3% (p = 0.004) after genipin fixation. Thus, maximal forward flow velocity was increased by 33.3% (p = 0.008) after glutaraldehyde fixation and by 52.8% (p = 0.001) after genipin fixation. The flow acceleration was consistent with a funnel shape of the fixed valves causing important flow contraction beyond the orifice (vena contracta). The papillary muscle force increased with apically posterior papillary muscle displacement by 20.4% (p = 0.001) and 101.5% (p <0.001) after glutaraldehyde and genipin fixation, respectively, and total regurgitant volume was increased by 91.6% (p <0.001) and 117.3% (p <0.001), respectively. The work required by the heart simulator to maintain a constant cardiac output at constant vascular resistance increased by 24.2% (p = 0.003) and 34.2% (p = 0.004) after glutaraldehyde and genipin fixation, respectively.
The present study shows that chemical fixation of porcine mitral valves adversely affects the hemodynamics of the valves, increasing overall workload. The effects were more severe after fixation with genipin than with glutaraldehyde. This suggests the need to explore other fixation agents to optimize valvular cardiac function. Cryopreservation had no detrimental effects on valvular hemodynamic performance.
近期进展表明，为优化瓣膜流体动力学，应考虑使用无支架生物人工二尖瓣异种移植物。固定过程会改变组织的力学性能。本研究调查固定后二尖瓣形态和血流动力学性能的变化。
切除猪二尖瓣并将其附着于生理环形环上。使用刚性透明左心模型在体外研究二尖瓣功能，该模型可提供横向和矢状面视图。最初的实验在生理条件下使用新鲜瓣膜进行。采用三种不同的乳头肌位置，并对每种位置进行记录。在戊二醛固定、京尼平固定和冷冻保存后，在维持心输出量的同时对瓣膜进行重新研究。通过固定前后瓣膜的详细解剖测量检测形态变化。从流体动力学压力和流量数据、高速摄像机、数字视频、多普勒超声以及三维乳头肌力测量中获取固定前后的性能特征。
经京尼平固定后瓣膜长度减少了18.5%（p<0.001），而经戊二醛固定后未减少。冷冻保存的瓣膜在保存后形态或流体动力学性能无统计学显著变化。戊二醛固定后正向血流开口面积减少了12.2%（p<0.001），京尼平固定后减少了32.3%（p = 0.004）。因此，戊二醛固定后最大正向血流速度增加了33.3%（p = 0.008），京尼平固定后增加了52.8%（p = 0.001）。血流加速与固定瓣膜的漏斗形状一致，导致孔口（缩窄处）后方出现重要的血流收缩。戊二醛和京尼平固定后，乳头肌力分别随着心尖后乳头肌位移增加了20.4%（p = 0.001）和101.5%（p<0.001），总反流体积分别增加了91.6%（p<0.001）和117.3%（p<0.001）。在恒定血管阻力下维持恒定心输出量时，心脏模拟器所需的功在戊二醛和京尼平固定后分别增加了24.2%（p = 0.003）和34.2%（p = 0.004）。
本研究表明，猪二尖瓣的化学固定会对瓣膜血流动力学产生不利影响，增加整体工作量。京尼平固定后的影响比戊二醛固定更严重。这表明需要探索其他固定剂以优化瓣膜心脏功能。冷冻保存对瓣膜血流动力学性能无有害影响。
