Hearts are usually procured from brain‐dead (BD) donors. However, brain death may induce hemodynamic instability, which may contribute to posttransplant graft dysfunction. We hypothesized that BD‐donor heart preservation with a conditioned medium (CM) from mesenchymal stem cells (MSCs) would improve graft function after transplantation. Additionally, we explored the PI3K pathway's potential role. Rat MSCs‐derived CM was used for conservation purposes. Donor rats were either exposed to sham operation or brain death by inflation of a subdural balloon‐catheter for 5.5 hours. Then, the hearts were explanted, stored in cardioplegic solution‐supplemented with either a medium vehicle (BD and sham), CM (BD + CM), or LY294002, an inhibitor of PI3K (BD + CM + LY), and finally transplanted. Systolic performance and relaxation parameters were significantly reduced in BD‐donors compared to sham. After transplantation, systolic and diastolic functions were significantly decreased, terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling (TUNEL)‐positive cells and endonuclease G positive cells were increased in the BD‐group compared to sham. Preservation of BD‐donor hearts with CM resulted in a recovery of systolic graft function (dP/dt_max: BD + CM: 3148 ± 178 vs BD: 2192 ± 94 mm Hg/s at 110 µL, P < .05) and reduced apoptosis. LY294002 partially lowered graft protection afforded by CM in the BD group. Our data suggest that PI3K/Akt pathway is not the primary mechanism of action of CM in improving posttransplant cardiac contractility and preventing caspase‐independent apoptosis.

中文翻译：

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用间充质干细胞条件培养基补充的保存液保存脑死亡供体心脏可改善移植后移植物的收缩力

心脏通常是从脑死亡 (BD) 捐赠者那里获得的。然而，脑死亡可能引起血流动力学不稳定，这可能导致移植后移植物功能障碍。我们假设使用来自间充质干细胞 (MSC) 的条件培养基 (CM) 保存 BD 供体心脏会改善移植后的移植物功能。此外，我们探索了 PI3K 通路的潜在作用。大鼠 MSCs 衍生的 CM 用于保护目的。供体大鼠通过硬膜下球囊导管充气 5.5 小时进行假手术或脑死亡。然后，心脏被移植，储存在补充有介质载体（BD 和假手术）、CM（BD + CM）或 PI3K 抑制剂 LY294002（BD + CM + LY）的心脏停搏液中，最后进行移植。与假手术相比，BD 供体的收缩性能和松弛参数显着降低。移植后，与假手术相比，BD 组的收缩和舒张功能显着下降，末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记 (TUNEL) 阳性细胞和核酸内切酶 G 阳性细胞增加。用 CM 保存 BD 供体心脏导致收缩移植物功能恢复（dP/dt_最大值：BD + CM：3148 ± 178 对比 BD：2192 ± 94 mm Hg/s 在 110 µL，P  < .05) 和细胞凋亡减少。LY294002 部分降低了 BD 组中 CM 提供的移植物保护。我们的数据表明 PI3K/Akt 通路不是 CM 改善移植后心肌收缩力和防止 caspase 非依赖性细胞凋亡的主要作用机制。