Jacob Matthias, Paul Oliver, Mehringer Laurenz, Chappell Daniel, Rehm Markus, Welsch Ulrich, Kaczmarek Ingo, Conzen Peter, Becker Bernhard F
Clinic of Anesthesiology, Ludwig-Maximilians-Universitaet Muenchen, Munich, Germany.
Transplantation. 2009 Apr 15;87(7):956-65. doi: 10.1097/TP.0b013e31819c83b5.
Major causes of death after heart transplantation are right ventricular pump failure and, chronically, cardiac allograft vasculopathy. Traditional preservation techniques focus on immediate cardioplegia, without particularly considering vascular demands. Recently, the endothelial surface layer, composed of the endothelial glycocalyx and plasma proteins, was discovered to play a major role in vascular barrier function, edema formation, and leukocyte-to-endothelial interaction. The impact of augmenting a traditional preservation solution with plasma colloid albumin was therefore investigated.
Guinea pig hearts underwent cold ischemic storage for 4 hr using Bretschneider's solution (histidine-tryptophan-ketoglutarate [HTK]) without and with augmentation with 1 g% human albumin. After reperfusion, intracoronary adhesion of polymorphonuclear granulocytes, edema formation, left and right heart performance of pressure-to-volume work, and glycocalyx shedding were assessed.
Intracoronary retention of leukocytes was doubled in the traditional group (36.4+/-6.6%), whereas it remained at basal values after albumin preservation (23.5+/-2.4%; P<0.05). Addition of albumin to HTK significantly decreased edema formation (wet to dry weight ratio 6.9+/-0.1 vs. 7.2+/-0.2; P<0.05). Although left heart performance was comparable, right heart cardiac output was doubled in hearts having received HTK containing albumin versus HTK alone (94+/-14 vs. 50+/-11 mL/min/g; P<0.05). Glycocalyx shedding was significantly reduced when the hearts were stored under albumin protection.
Augmenting HTK with human albumin improves endothelial integrity and heart performance after 4 hr cold ischemia, because of a marked protection of the endothelial glycocalyx. For the prevention of acute and chronic graft failure, the glycocalyx might represent a new target.
心脏移植术后的主要死亡原因是右心室泵衰竭,长期来看是心脏移植血管病变。传统的保存技术侧重于即刻心脏停搏,而没有特别考虑血管需求。最近发现,由内皮糖萼和血浆蛋白组成的内皮表面层在血管屏障功能、水肿形成以及白细胞与内皮细胞相互作用中起主要作用。因此,研究了用血浆胶体白蛋白增强传统保存液的影响。
豚鼠心脏使用布雷施奈德溶液(组氨酸 - 色氨酸 - 酮戊二酸 [HTK])进行4小时冷缺血保存,分别使用不含和添加1g%人白蛋白的HTK溶液。再灌注后,评估多形核粒细胞的冠状动脉内黏附、水肿形成、左右心室压力 - 容积功的心脏功能以及糖萼脱落情况。
传统组白细胞的冠状动脉内滞留量增加了一倍(36.4±6.6%),而白蛋白保存后保持在基础值(23.5±2.4%;P<0.05)。向HTK中添加白蛋白显著减少了水肿形成(湿重与干重比为6.9±0.1对7.2±0.2;P<0.05)。虽然左心室功能相当,但接受含白蛋白的HTK溶液保存的心脏右心输出量是仅接受HTK溶液保存心脏的两倍(94±14对50±11 mL/min/g;P<0.05)。在白蛋白保护下保存心脏时,糖萼脱落显著减少。
用人类白蛋白增强HTK可改善4小时冷缺血后的内皮完整性和心脏功能,这是由于对内皮糖萼有显著保护作用。对于预防急慢性移植物衰竭,糖萼可能是一个新的靶点。