A new solution for life without blood. Asanguineous low-flow perfusion of a whole-body perfusate during 3 hours of cardiac arrest and profound hypothermia.
A new solution for life without blood. Asanguineous low-flow perfusion of a whole-body perfusate during 3 hours of cardiac arrest and profound hypothermia.
复制标题
无血生命的新解决方案。
DOI：
10.1161/01.cir.91.2.431
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发表时间：
1995
期刊：
影响因子：
37.8
通讯作者：
Maroon,JC
中科院分区：
文献类型：
--
作者：
Taylor,MJ;Bailes,JE;Elrifai,AM;Shih,SR;Teeple,E;Leavitt,ML;Baust,JG;Maroon,JC
背景低温对预防缺血性损伤的益处是众所周知的，但其在需要循环停止的手术期间用于保护全身的手术中的应用目前限于在15°C下使用50%血液稀释<1小时。与以前的方法有很大不同，我们在犬模型中开发了一种低流量灌注和心脏骤停的无血血液替代技术。我们的方法是设计一种低温血液替代品，在几个小时的无血灌注期间保护大脑和内脏器官。两种不同的解决方案已被设计，以满足单独的要求，在procedure.Methods和ResultsWith使用的体外心脏搭桥术，14只成年狗在冷却过程中放血; 11只狗血液替代使用组合的“清洗”和“维护”的解决方案（组1），和3只狗灌注整个“清洗”解决方案单独作为对照（组2）。心脏骤停后，溶液连续循环3\batchmode\documentclass[fleqn，10 pt，legalpaper]{article} \usepackage {amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \开始{document} \（\frac{1}{2}\）通过体外泵（流速，40至85 mL · kg−1· min−1;平均动脉血压，25至40 mm Hg）记录结束{document}小时。将温度保持在<10°C（最低点，6.6±0.1°C）3小时，并且在受控复温和自体输血之前将血细胞比容保持在<1%。在实验组中，心脏总是在11°C至27°C的温度范围内自发启动，8只动物长期存活（目前范围为14至110周），没有任何可检测到的神经功能缺损。相比之下，2只对照动物在广泛和积极的心脏复苏努力后存活;手术后，它们表现出短暂的运动和感觉缺陷约1周。生化和血液学参数评价显示，第1组中的酶（例如，脑、肝、心脏）仅出现一过性和无关紧要的升高，而第2组中的升高幅度明显更大。例如，第1组的乳酸脱氢酶术后即刻值（平均值±SEM）为114±10，第2组为490±210（P<.03）; SGOT值为93±18，第1组为734±540，第2组为734±540（P<.05）。第1天，肌酸激酶（CK）的第1组值为7841±2307，第2组为71 550±2658（P=.03），CK-BB的第1组值为108±22，第2组为617±154（P=.03）。使用缺陷评分（NDS）进行的神经学评价基于改良的格拉斯哥昏迷量表评分：0，正常; 1，轻微异常; 2，虚弱; 3，瘫痪; 4，昏迷; 5，死亡。术后第1天和第2天，实验组的NDS（平均值±SEM）为0±0，对照组为1.5±0.5。术后第3天和第7天，第1组的NDS为0±0，第2组为1.0±1.0。结论用“细胞内型”维持液治疗的狗的神经功能恢复更快，支持了生化数据显示这种类型的血液替代品延长低温心脏骤停程序的安全限度至>3小时的益处。
BackgroundThe benefits of hypothermia for preventing ischemic injury are well known, but its application in surgery to protect the whole body during procedures requiring circulatory arrest is currently limited to <1 hour at 15°C using 50% hemodilution. In a significant departure from previous methods, we have developed a technique of asanguineous blood substitution with low-flow perfusion and cardiac arrest at <10°C in a canine model. Our approach has been to design a hypothermic blood substitute that would protect the brain and visceral organs during several hours of bloodless perfusion. Two different solutions have been designed to fulfill separate requirements in the procedure.Methods and ResultsWith the use of extracorporeal cardiac bypass, 14 adult dogs were exsanguinated during cooling; 11 dogs were blood substituted using in combination the “purge” and “maintenance” solutions (group 1), and 3 dogs were perfused throughout with the “purge” solution alone as controls (group 2). After cardiac arrest, the solutions were continuously circulated for 3\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{1}{2}\) \end{document} hours by the extracorporeal pump (flow rate, 40 to 85 mL · kg−1· min−1; mean arterial blood pressure, 25 to 40 mm Hg). The temperature was maintained at <10°C (nadir, 6.6±0.1°C) for 3 hours, and the hematocrit was kept at <1% before controlled rewarming and autotransfusion. In the experimental group, the heart always started spontaneously in the temperature range of 11°C to 27°C, and 8 animals have survived long-term (current range, 14 to 110 weeks) without any detectable neurological deficit. In contrast, two control animals survived after extensive and aggressive cardiac resuscitation efforts; after surgery they exhibited transient motor and sensory deficits for approximately 1 week. Evaluation of biochemical and hematological parameters showed only a transient and inconsequential elevation in enzymes (eg, brain, liver, cardiac) in group 1 compared with the markedly greater elevations in group 2. For example, immediate postoperative values (mean±SEM) for lactate dehydrogenase were 114±10 for group 1 versus 490±210 for group 2 (P<.03); for SGOT, values were 93±18 for group 1 versus 734±540 for group 2 (P<.05). On day 1 for creatine kinase (CK), the group 1 value was 7841±2307 versus 71 550±2658 for group 2 (P=.03), and for CK-BB, the group 1 value was 108±22 versus 617±154 for group 2 (P=.03). Neurological evaluation using deficit scores (NDS) was based on a modification of the Glasgow Coma Scale score: 0, normal; 1, minimal abnormality; 2, weakness; 3, paralysis; 4, coma; and 5, death. At days 1 and 2 after surgery, NDS (mean±SEM) were 0±0 for the experimental group versus 1.5±0.5 for the control group. At days 3 and 7 after surgery, NDS were 0±0 for group 1 versus 1.0±1.0 for group 2.ConclusionsThe faster neurological recovery of dogs treated with the “intracellular-type” maintenance solution supports the biochemical data showing the benefits of this type of blood substitute for extending the safe limits of hypothermic cardiac arrest procedures to >3 hours.