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用于体内通用组织保存的保存液设计:在深度低温心脏骤停临床前模型中的疗效验证

Design of preservation solutions for universal tissue preservation in vivo: demonstration of efficacy in preclinical models of profound hypothermic cardiac arrest.

作者信息

Taylor M J, Rhee P, Chen Z, Alam H B

机构信息

Organ Recovery Systems, Charleston, SC 29403, USA.

出版信息

Transplant Proc. 2005 Jan-Feb;37(1):303-7. doi: 10.1016/j.transproceed.2004.12.024.

Abstract

The design of new solutions for the universal preservation of tissues is a quest that would facilitate multiple-organ harvesting from organ donors since current preservation solutions do not provide optimum preservation for all organs. In contrast, a new approach to bloodless surgery using hypothermic blood substitution (HBS) to protect the whole body during profound hypothermic circulatory arrest (clinical suspended animation) has focused on the development of a hybrid solution design with the objective of providing universal tissue preservation. In this study, a porcine model of uncontrolled lethal hemorrhage was employed. A combination of two new solutions, maintenance and purge, was used in a cardiopulmonary bypass (CPB) technique to affect profound hypothermia and prolonged cardiac arrest (60 min), with resuscitation after surgical repair of the vascular deficit induced to affect exsanguination. After rewarming and recovery, pigs were monitored for 6 weeks for neurological deficits, cognitive function (learning new skills), and organ dysfunction. All the normothermic control animals died (n = 10), whereas 90% (9 of 10) in the HBS group survived (P < .05). Moreover, all of the survivors were neurologically intact, displayed normal learning and memory capability, and had no long-term organ dysfunction. Histology of brains after 6 weeks revealed no ischemic damage in marked contrast to control animals, which all showed diffuse ischemic damage. The demonstrated efficacy of these synthetic, acellular HBS solutions for protection of all the tissues in the body during clinical suspended animation justifies their consideration for multiple-organ harvesting from cadaveric and living donors.

摘要

设计用于组织通用保存的新解决方案是一项探索任务,这将有助于从器官捐赠者获取多个器官,因为目前的保存溶液不能为所有器官提供最佳保存效果。相比之下,一种使用低温血液置换(HBS)在深度低温循环停止(临床假死)期间保护全身的无血手术新方法,专注于开发一种混合溶液设计,目标是实现通用组织保存。在本研究中,采用了猪的非控制性致死性出血模型。在体外循环(CPB)技术中使用两种新溶液(维持液和清洗液)的组合,以实现深度低温和延长心脏停搏(60分钟),在修复导致失血的血管缺损后进行复苏。复温并恢复后,对猪进行6周的监测,观察神经功能缺损、认知功能(学习新技能)和器官功能障碍情况。所有正常体温的对照动物均死亡(n = 10),而HBS组90%(10只中的9只)存活(P <.05)。此外,所有存活者神经功能均完好,显示出正常的学习和记忆能力,且无长期器官功能障碍。6周后脑组织学检查显示,与所有均表现出弥漫性缺血损伤的对照动物形成鲜明对比,未发现缺血损伤。这些合成的无细胞HBS溶液在临床假死期间对保护体内所有组织的有效性,证明它们值得考虑用于从尸体和活体捐赠者获取多个器官。

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