Department of General Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Transpl Int. 2012 Jun;25(6):696-706. doi: 10.1111/j.1432-2277.2012.01469.x. Epub 2012 Apr 4.
Since prolonged cold preservation of the heart deteriorates the outcome of heart transplantation, a more protective preservation solution is required. We therefore developed a new solution, named Dsol, and examined whether Dsol, in comparison to UW, could better inhibit myocardial injury resulting from prolonged cold preservation. Syngeneic heterotopic heart transplantation in Lewis rats was performed after cold preservation with UW or Dsol for 24 or 36 h. In addition to graft survival, myocardial injury, ATP content, and Ca(2+) -dependent proteases activity were assessed in the 24-h preservation group. The cytosolic Ca(2+) concentration of H9c2 cardiomyocytes after 24-h cold preservation was assessed. Dsol significantly improved 7-day graft survival after 36-h preservation. After 24-h preservation, Dsol was associated with significantly faster recovery of ATP content and less activation of calpain and caspase-3 after reperfusion. Dsol diminished graft injury significantly, as revealed by the lower levels of infarction, apoptosis, serum LDH and AST release, and graft fibrosis at 7-day. Dsol significantly inhibited Ca(2+) overload during cold preservation. Dsol inhibited myocardial injury and improved graft survival by suppressing Ca(2+) overload during the preservation and the activation of Ca(2+) -dependent proteases. Dsol is therefore considered a better alternative to UW to ameliorate the outcome of heart transplantation.
由于心脏的长时间冷藏会导致心脏移植的效果恶化,因此需要更具保护作用的保存液。因此,我们开发了一种新的溶液,称为 Dsol,并研究了 Dsol 是否比 UW 更能抑制长时间冷藏引起的心肌损伤。在 UW 或 Dsol 冷保存 24 或 36 小时后,进行了 Lewis 大鼠的同基因异位心脏移植。除了移植物存活外,还在 24 小时保存组中评估了心肌损伤、ATP 含量和 Ca(2+)依赖性蛋白酶活性。评估了 H9c2 心肌细胞在 24 小时冷保存后的细胞浆 Ca(2+)浓度。Dsol 显著提高了 36 小时保存后 7 天移植物的存活率。在 24 小时保存后,与 UW 相比,Dsol 与再灌注后 ATP 含量更快恢复以及钙蛋白酶和半胱天冬酶-3 的激活减少有关。Dsol 显著减轻了移植物损伤,表现在 7 天时梗死、凋亡、血清 LDH 和 AST 释放以及移植物纤维化程度降低。Dsol 显著抑制了冷保存过程中的 Ca(2+)超载。Dsol 通过抑制保存过程中的 Ca(2+)超载和 Ca(2+)依赖性蛋白酶的激活来抑制心肌损伤并改善移植物存活。因此,Dsol 被认为是 UW 的更好替代品,可改善心脏移植的结果。