Department of Surgery, University of Manitoba, Winnipeg, MB, Canada.
Cardiac Sciences Program, I.H. Asper Clinical Research Institute, Winnipeg Regional Health Authority and St. Boniface Hospital, Winnipeg, MB, Canada.
Methods Mol Biol. 2020;2110:227-243. doi: 10.1007/978-1-0716-0255-3_15.
Millions of patients with valvular heart disease have benefitted from heart valve replacement since the procedure was first introduced in the 1960s; however, there are still many patients who get early structural valve deterioration (SVD) of their bioprosthetic heart valves (BHV). BHV are porcine, bovine, or equine tissues that have been glutaraldehyde fixed to preserve the tissue and presumably make the tissue immunologically inert. These glutaraldehyde-fixed BHV with anti-calcification treatments last long periods of time in older adults but develop early SVD in younger patients. The consensus at present is that the early SVD in younger patients is due to more "wear and tear" of the valves and higher calcium turnover in younger patients. However, as younger patients likely have a more robust immune system than older adults, there is a new hypothesis that BHV xenografts may undergo xenograft rejection, and this may contribute to the early SVD seen in younger patients.At present, the technology to noninvasively study in vivo whether an implanted BHV in a human patient is undergoing rejection is not available. Thus, a small animal discordant xenotransplant model in young rodents (to match the young patient getting a pig/bovine/equine BHV) was developed to study whether the hypothesis that glutaraldehyde-fixed BHV undergo xenograft rejection had any merit. In this chapter, we describe our model and its merits and the results of our investigations. Our work provides clear evidence of xenograft rejection in glutaraldehyde-fixed tissue, and our small animal model offers an opportunity to study this process in detail.
自 20 世纪 60 年代首次引入心脏瓣膜置换术以来，数以百万计的瓣膜性心脏病患者从中受益；然而，仍有许多患者的生物瓣心脏瓣膜（BHV）发生早期结构性瓣膜退化（SVD）。BHV 是经过戊二醛固定以保存组织并使组织具有免疫惰性的猪、牛或马组织。经过戊二醛固定和抗钙化处理的 BHV 在老年患者中可以持续很长时间，但在年轻患者中会较早出现 SVD。目前的共识是，年轻患者的早期 SVD 是由于瓣膜的“磨损”更多，以及年轻患者的钙周转率更高。然而，由于年轻患者的免疫系统可能比老年患者更强大，因此出现了一种新的假设，即 BHV 异种移植物可能会发生异种排斥，这可能导致年轻患者中出现早期 SVD。目前，尚无技术可以无创地研究体内人类患者植入的 BHV 是否发生排斥反应。因此，开发了一种年轻啮齿动物的小型动物不相容异种移植模型（与接受猪/牛/马 BHV 的年轻患者相匹配），以研究戊二醛固定的 BHV 是否发生异种排斥反应的假设是否有价值。在本章中，我们描述了我们的模型及其优点，以及我们的研究结果。我们的工作提供了戊二醛固定组织中发生异种排斥反应的明确证据，并且我们的小动物模型为详细研究这一过程提供了机会。
