Department of Microbiology and Immunology, Western University, London, ON N6A 5C1, Canada.
Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Centre, London, ON N6A 5A5, Canada.
Int J Mol Sci. 2021 Jul 2;22(13):7180. doi: 10.3390/ijms22137180.
The use of blood for normothermic and subnormothermic kidney preservation hinders the translation of these approaches and promising therapeutics. This study evaluates whether adding hydrogen sulfide donor AP39 to Hemopure, a blood substitute, during subnormothermic perfusion improves kidney outcomes. After 30 min of renal pedicle clamping, porcine kidneys were treated to 4 h of static cold storage (SCS-4 °C) or subnormothermic perfusion at 21 °C with Hemopure (H-21 °C), Hemopure + 200 nM AP39 (H200nM-21 °C) or Hemopure + 1 µM AP39 (H1µM-21 °C). Then, kidneys were reperfused with Hemopure at 37 °C for 4 h with metabolic support. Perfusate composition, tissue oxygenation, urinalysis and histopathology were analyzed. During preservation, the H200nM-21 °C group exhibited significantly higher urine output than the other groups and significantly higher tissue oxygenation than the H1µM-21 °C group at 1 h and 2h. During reperfusion, the H200nM-21 °C group exhibited significantly higher urine output and lower urine protein than the other groups. Additionally, the H200nM-21 °C group exhibited higher perfusate pO levels than the other groups and significantly lower apoptotic injury than the H-21 °C and the H1µM-21 °C groups. Thus, subnormothermic perfusion at 21 °C with Hemopure + 200 nM AP39 improves renal outcomes. Additionally, our novel blood-free model of ex vivo kidney preservation and reperfusion could be useful for studying other therapeutics.
在常温及亚低温条件下保存肾脏时使用血液会阻碍这些方法和有前途的治疗方法的转化。本研究评估了在亚低温灌注过程中向血液代用品 Hemopure 中添加硫化氢供体 AP39 是否可以改善肾脏的保存效果。在肾蒂夹闭 30 分钟后，将猪的肾脏在 4 小时的静态冷保存（4°C，SCS-4°C）或在 21°C 下进行亚低温灌注，使用 Hemopure（H-21°C）、Hemopure+200 nM AP39（H200nM-21°C）或 Hemopure+1 µM AP39（H1µM-21°C）。然后，在 37°C 下使用 Hemopure 进行 4 小时的再灌注，并进行代谢支持。分析灌流液成分、组织氧合、尿液分析和组织病理学。在保存过程中，与其他组相比，H200nM-21°C 组在 1 小时和 2 小时时的尿量明显更高，组织氧合明显更高。在再灌注过程中，与其他组相比，H200nM-21°C 组的尿量更多，尿蛋白更低。此外，与其他组相比，H200nM-21°C 组的灌流液 pO 水平更高，与 H-21°C 和 H1µM-21°C 组相比，凋亡损伤明显更低。因此，在 21°C 下使用 Hemopure+200 nM AP39 进行亚低温灌注可以改善肾脏的保存效果。此外，我们开发的新型无血体外肾脏保存和再灌注模型可能有助于研究其他治疗方法。
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