Menasché P, Pradier F, Grousset C, Peynet J, Mouas C, Bloch G, Piwnica A
Department of Cardiovascular Surgery, Hôpital Lariboisière, Paris, France.
J Thorac Cardiovasc Surg. 1993 Feb;105(2):353-63.
In the course of cardiac transplantation, donor hearts undergo a four-step sequence of events (arrest, cold storage, global ischemia during implantation, and reperfusion) during which myocardial damage can occur. We tested the hypothesis that the functional recovery of these hearts could be improved by exposure to two interdependently formulated preservation solutions throughout this four-step sequence. Solution I was used as a perfusion and storage medium during the first three steps, and solution II served as a modified reperfusate. The two solutions share the following principles of formulation: prevention of cell swelling (high concentrations of mannitol, a myocardium-specific impermeant) calcium overload (ionic manipulations), and oxidative damage (reduced glutathione) and enhancement of anaerobic energy production (glutamate). The two solutions differ with respect to the calcium content and buffering capacity. One hundred rat hearts perfused with isolated isovolumic buffer were subjected to cardioplegic arrest; cold (2 degrees C) storage for 5 hours, global ischemia at 15 degrees C for 1 hour, and normothermic reperfusion for 1 additional hour. In a first series of experiments (70 hearts), our kit of solutions was compared with six clinical preservation regimens that involved cardiac arrest with St. Thomas' Hospital or University of Wisconsin solutions followed by storage of the hearts in saline, Euro-Collins, St. Thomas' Hospital, or University of Wisconsin solutions. In a second series of experiments (30 hearts), the effects of the kit were more specifically investigated in relation to two types of additive--oncotic agents (dextran) and thiol-based antioxidants (reduced glutathione and N-acetyl-L-cysteine). According to comparisons of maximal rate of ventricular pressure increase and left ventricular compliance after reperfusion, the best myocardial protection was afforded by our kit of solutions. The addition of dextran during storage did not provide additional protection. Conversely, the omission of reduced glutathione was clearly detrimental; the replacement of reduced glutathione with N-acetyl-L-cysteine failed to improve recovery beyond that provided by antioxidant-free solutions, thereby suggesting the importance, in this model, of an anti-free radical compound that, like reduced glutathione, is operative extracellularly. We conclude that the preservation of heart transplants can be improved with the sequential use of two closely interrelated solutions, the formulations of which integrate the basic principles of organ preservation with those of myocardium-specific metabolism.
在心脏移植过程中，供体心脏会经历四个连续的事件阶段（停搏、冷藏、植入过程中的整体缺血以及再灌注），在此期间可能会发生心肌损伤。我们验证了这样一个假设：在这四个阶段中，通过使用两种相互依存配制的保存溶液，可以改善这些心脏的功能恢复。溶液I在前三个阶段用作灌注和储存介质，溶液II用作改良的再灌注液。这两种溶液具有以下共同的配制原则：防止细胞肿胀（高浓度甘露醇，一种心肌特异性非通透剂）、钙超载（离子调控）、氧化损伤（还原型谷胱甘肽）以及增强无氧能量产生（谷氨酸）。两种溶液在钙含量和缓冲能力方面有所不同。将100个用离体等容缓冲液灌注的大鼠心脏进行心脏停搏；在2℃冷藏5小时，在15℃整体缺血1小时，然后再进行常温再灌注1小时。在第一系列实验（70个心脏）中，将我们的溶液套装与六种临床保存方案进行了比较，这六种方案包括使用圣托马斯医院溶液或威斯康星大学溶液进行心脏停搏，随后将心脏保存在生理盐水、欧洲柯林斯溶液、圣托马斯医院溶液或威斯康星大学溶液中。在第二系列实验（30个心脏）中，更具体地研究了该溶液套装与两种添加剂——胶体渗透压剂（右旋糖酐）和基于硫醇的抗氧化剂（还原型谷胱甘肽和N-乙酰-L-半胱氨酸）相关的效果。根据再灌注后心室压力最大上升速率和左心室顺应性的比较，我们的溶液套装提供了最佳的心肌保护。在储存期间添加右旋糖酐并未提供额外的保护。相反，省略还原型谷胱甘肽显然是有害的；用N-乙酰-L-半胱氨酸替代还原型谷胱甘肽未能使恢复情况比无抗氧化剂的溶液有所改善，从而表明在该模型中，一种像还原型谷胱甘肽一样在细胞外起作用的抗自由基化合物的重要性。我们得出结论，通过依次使用两种密切相关的溶液可以改善心脏移植的保存效果，这两种溶液的配制将器官保存的基本原理与心肌特异性代谢的原理结合在了一起。
