4.7 Article

S-Nitrosylated hemoglobin predicts organ yield in neurologically-deceased human donors

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SCIENTIFIC REPORTS
卷 12, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41598-022-09933-z

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资金

  1. Roche Organ Transplant Research Foundation (Meggen, Switzerland) [61800655]
  2. AHA-Allen Brain Health Initiative [19PABHI34580006]
  3. Eppley Foundation (New York, NY) Enduring Hearts (Marietta, GA)
  4. Additional Ventures (Palo Alto, CA)
  5. US Army Medical Research and Materiel Command [W81XWH-16-1-0520]

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Based on clinical findings, SNO-Hb levels are significantly decreased after brain death, which negatively impacts StO(2) and reduces the number of organs available for transplantation from DNC human donors. The inclusion of exogenous S-nitrosylating agents can increase organ yields and quality for transplantation.
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(2)). Based on various pre-clinical studies, we hypothesized that brain death (BD) would decrease post-mortem SNO-Hb levels to negatively-impact StO(2) 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 center dot 003) and remained reduced for the duration of the monitoring period. There was a positive correlation between SNO-Hb and StO(2) (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(2) 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.

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