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使用基于新型聚乙二醇化牛血红蛋白灌注液的溶液在跳动状态下进行延长的离体心肌保存。

Extended ex vivo myocardial preservation in the beating state using a novel polyethylene glycolated bovine hemoglobin perfusate based solution.

作者信息

Jones Blanding U, Serna Dan L, Smulowitz Peter, Connolly Peter, Farber Adam, Beckham Gerry, Shrivastava Vineet, Kahwaji Chad, Steward Earl, Purdy Ralph E, Parker W Lane, Ages Berend, Milliken Jeffrey C

机构信息

Division of Cardiothoracic Surgery, Department of Pharmacology, University of California, Irvine, Medical Center, Orange, California 92868, USA.

出版信息

ASAIO J. 2003 Jul-Aug;49(4):388-94.

Abstract

Cardiac preservation for transplantation is generally limited by ischemic hypothermic storage of 4-6 hours. Earlier studies in the authors' laboratory have demonstrated that hypothermic perfusion preservation using a novel oxygen carrying hemoglobin solution may extend preservation times to 8 hours and decrease ischemic injury. The purpose of this study was to compare extended cardiac function after 12 and 24 hours of continuous hypothermic perfusion with a polyethylene glycolated bovine hemoglobin perfusate (PEG-Hb) solution to the clinical standard of hypothermic ischemic preservation. The hearts of 54 anesthetized and intubated New Zealand White rabbits were harvested after cold cardioplegic arrest. Group I (n = 12) hearts were perfused with a PEG-Hb solution at 20 degrees C and 30 mm Hg for 24 hours. Group II (n = 10) hearts were preserved similarly with PEG-Hb for 12 hours. Group III (n = 12) hearts were preserved for 8 hours with PEG-Hb; Group IV (n = 10) were preserved by cold ischemic storage for 4 hours at 4 degrees C; and Group V (n = 10) were tested after fresh extirpation. Left ventricular (LV) function was measured in the nonworking state at 15 minute, 1 hour, and 2 hour intervals after transfer to a standard crystalloid Langendorff circuit. Developed LV pressure at 0.5 ml LV volume was superior in Group II at early time points, yet it was similar in all preserved groups at 2 hours. +dP/dt(max) at 0.5 ml LV volume was consistent at all time points and greater in PEG-Hb preserved groups compared with Group V. -dP/dt(max) at 0.5 ml LV volume was significantly greater in Groups II and III compared with Group V initially (p < 0.05), but all were similar at the end of testing. Continuous perfusion preservation of rabbit hearts for time increments up to 24 hours with this novel PEG-Hb solution at 30 mm Hg and 20 degrees C yields LV function that is similar to 4 hours of ischemic hypothermic storage. Extended cardiac perfusion preservation with this PEG-Hb solution deserves further investigation in large animal transplant models.

摘要

心脏移植的保存通常受限于4至6小时的低温缺血保存。作者实验室早期的研究表明,使用新型携氧血红蛋白溶液进行低温灌注保存可将保存时间延长至8小时,并减少缺血损伤。本研究的目的是比较用聚乙二醇化牛血红蛋白灌注液(PEG-Hb)连续低温灌注12小时和24小时后的心脏功能延长情况与低温缺血保存的临床标准。54只麻醉并插管的新西兰白兔心脏在冷停搏后被摘取。第一组(n = 12)心脏在20℃和30mmHg下用PEG-Hb溶液灌注24小时。第二组(n = 10)心脏用PEG-Hb以类似方式保存12小时。第三组(n = 12)心脏用PEG-Hb保存8小时;第四组(n = 10)在4℃下通过冷缺血保存4小时;第五组(n = 10)在新鲜摘取后进行测试。在转移到标准晶体Langendorff循环后,于15分钟、1小时和2小时间隔测量非工作状态下的左心室(LV)功能。在早期时间点,第二组在0.5ml左心室容积时的左心室舒张末压较高,但在2小时时所有保存组相似。在所有时间点,0.5ml左心室容积时的 +dP/dt(max) 一致,与第五组相比,PEG-Hb保存组更高。与第五组相比,第二组和第三组在0.5ml左心室容积时的 -dP/dt(max) 最初显著更高(p < 0.05),但在测试结束时所有组相似。用这种新型PEG-Hb溶液在30mmHg和20℃下对兔心脏进行长达24小时的连续灌注保存所产生的左心室功能类似于4小时的低温缺血保存。用这种PEG-Hb溶液进行延长心脏灌注保存值得在大型动物移植模型中进一步研究。

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