Ferng Alice S, Schipper David, Connell Alana M, Marsh Katherine M, Knapp Shannon, Khalpey Zain
Division of Cardiothoracic Surgery, Department of Surgery, University of Arizona College of Medicine, Tucson, AZ, USA.
Department of Physiological Sciences, University of Arizona College of Medicine, Tucson, AZ, USA.
J Cardiothorac Surg. 2017 Jan 26;12(1):7. doi: 10.1186/s13019-017-0564-x.
Heart transplantation remains the gold standard for end-stage heart failure, with current ex vivo organ storage times limited to 4 to 6 h before critical tissue damage occurs. Many preservation solutions exist in an attempt to limit both ischemic and reperfusion damage. In order to compare the effects of various storage solutions, mitochondrial function can be used to provide a sensitive analysis of cellular metabolic function.
Experimental plates were seeded with cardiac myoblasts and kept in suspended animation for either 4 or 8 h at either 4 or 21 °C, in Celsior®, Perfadex®, or Somah storage solutions. Cells were then reanimated for 1 h at 37 °C to simulate a reperfusion or clinical transplant scenario. Cellular bioenergetics were measured immediately thereafter to examine biochemical differences between preservation solutions and their effectiveness on preserving metabolic function.
The oxygen consumption rates of Somah solution were significantly higher than Celsior® and Perfadex® at 4 °C, with the exception of Perfadex® at 4 for 4 h. This effect was sustained up to 8 h. At 21 °C, oxygen consumption rates of Somah solution are significantly higher than Celsior® and Perfadex® at basal conditions after 4 h, but this effect is not sustained after 8 h.
The purpose of this experiment was to study the efficacy of various preservation solutions on a mitochondrial level. The significantly higher oxygen consumption rates of Somah at 4 °C suggests that Somah solution may have the ability to protect cellular mitochondrial integrity, improve transplanted organ function by reducing ischemic-reperfusion injury, and thereby improve transplant outcomes. Given that Somah offers benefits over Celsior® and Perfadex® at 4 °C, it should be a target in future organ preservation solution research.
心脏移植仍然是终末期心力衰竭的金标准,目前离体器官保存时间限制在关键组织损伤发生前4至6小时。存在多种保存溶液以试图限制缺血和再灌注损伤。为了比较各种保存溶液的效果,线粒体功能可用于对细胞代谢功能进行敏感分析。
将心肌母细胞接种到实验板上,并在4℃或21℃下于Celsior®、Perfadex®或Somah保存溶液中进行4或8小时的假死状态保存。然后将细胞在37℃下复苏1小时以模拟再灌注或临床移植情况。此后立即测量细胞生物能量学,以检查保存溶液之间的生化差异及其对保存代谢功能的有效性。
在4℃时,除了4小时的Perfadex®外,Somah溶液的氧消耗率显著高于Celsior®和Perfadex®。这种效果持续到8小时。在21℃时,4小时后基础条件下Somah溶液的氧消耗率显著高于Celsior®和Perfadex®,但8小时后这种效果未持续。
本实验的目的是研究各种保存溶液在线粒体水平上的功效。Somah在4℃时显著更高的氧消耗率表明,Somah溶液可能有能力保护细胞线粒体完整性,通过减少缺血-再灌注损伤来改善移植器官功能,从而改善移植结果。鉴于Somah在4℃时比Celsior®和Perfadex®更具优势,它应成为未来器官保存溶液研究的目标。