Institute for Transformative Molecular Medicine, School of Medicine Case Western Reserve University, Cleveland, OH, USA.
Department of Anesthesiology and Perioperative Medicine, School of Medicine Case Western Reserve University, Cleveland, OH, USA.
Sci Rep. 2022 Apr 22;12(1):6639. doi: 10.1038/s41598-022-09933-z.
Current human donor care protocols following death by neurologic criteria (DNC) can stabilize macro-hemodynamic parameters but have minimal ability to preserve systemic blood flow and microvascular oxygen delivery. S-nitrosylated hemoglobin (SNO-Hb) within red blood cells (RBCs) is the main regulator of tissue oxygenation (StO). Based on various pre-clinical studies, we hypothesized that brain death (BD) would decrease post-mortem SNO-Hb levels to negatively-impact StO and reduce organ yields. We tracked SNO-Hb and tissue oxygen in 61 DNC donors. After BD, SNO-Hb levels were determined to be significantly decreased compared to healthy humans (p = 0·003) and remained reduced for the duration of the monitoring period. There was a positive correlation between SNO-Hb and StO (p < 0.001). Furthermore, SNO-Hb levels correlated with and were prognostic for the number of organs transplanted (p < 0.001). These clinical findings provide additional support for the concept that BD induces a systemic impairment of S-nitrosylation that negatively impacts StO and reduces organ yield from DNC human donors. Exogenous S-nitrosylating agents are in various stages of clinical development. The results presented here suggest including one or more of these agents in donor support regimens could increase the number and quality of organs available for transplant.
目前,根据神经标准(DNC)死亡后的人类供体护理方案可以稳定宏观血液动力学参数,但几乎没有能力维持全身血流和微血管氧输送。红细胞(RBC)中的 S-亚硝基化血红蛋白(SNO-Hb)是组织氧合(StO)的主要调节剂。基于各种临床前研究,我们假设脑死亡(BD)会降低死后 SNO-Hb 水平,从而对 StO 产生负面影响,并降低器官产量。我们跟踪了 61 名 DNC 供体的 SNO-Hb 和组织氧。与健康人相比,BD 后 SNO-Hb 水平明显降低(p=0.003),并且在监测期间持续降低。SNO-Hb 与 StO 之间存在正相关(p<0.001)。此外,SNO-Hb 水平与移植器官数量相关,并且具有预后意义(p<0.001)。这些临床发现为以下概念提供了额外的支持,即 BD 会引起 S-亚硝化的全身性损伤,从而对 StO 产生负面影响,并降低 DNC 人类供体的器官产量。外源性 S-亚硝酰化剂处于不同的临床开发阶段。这里提出的结果表明,在供体支持方案中包含一种或多种这些试剂可能会增加可用于移植的器官数量和质量。