Evaluating the Effects of Subnormothermic Perfusion with AP39 in a Novel Blood-Free Model of Ex Vivo Kidney Preservation and Reperfusion.
Evaluating the Effects of Subnormothermic Perfusion with AP39 in a Novel Blood-Free Model of Ex Vivo Kidney Preservation and Reperfusion.
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DOI：
10.3390/ijms22137180
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发表时间：
2021-07-02
影响因子：
5.6
通讯作者：
Sener A
中科院分区：
文献类型：
--
作者：
Juriasingani S;Jackson A;Zhang MY;Ruthirakanthan A;Dugbartey GJ;Sogutdelen E;Levine M;Mandurah M;Whiteman M;Luke P;Sener A
血液用于常温和亚常温肾脏保存阻碍了这些方法和有前途的治疗方法的翻译。本研究评估在亚常温灌注期间，将硫化氢供体AP39加入血液替代品Hemopure中是否能改善肾脏预后。猪肾蒂夹持30 min后，分别用Hemopure （h -21°C）、Hemopure + 200nM AP39 （H200nM-21°C）或Hemopure + 1µM AP39 （H1µM-21°C）在21°C下进行4 h的静态冷藏（SCS-4°C）或亚常温灌注。然后，在代谢支持下，在37°C下用Hemopure再灌注肾脏4小时。对灌注液组成、组织氧合、尿液分析及组织病理学进行分析。在保存过程中，H200nM-21°C组在1 h和2h的尿量显著高于其他组，组织氧合显著高于H1µM-21°C组。再灌注时，H200nM-21°C组尿量明显高于其他组，尿蛋白明显低于其他组。此外，H200nM-21°C组灌注pO2水平高于其他组，凋亡损伤明显低于H-21°C和H1µM-21°C组。因此，在21°C下用Hemopure + 200 nM AP39进行亚常温灌注可改善肾脏预后。此外，我们的新型体外肾保存和再灌注无血模型可用于研究其他治疗方法。
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 pO2 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.
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影响因子：
5.5
作者：
Juriasingani S;Ruthirakanthan A;Richard-Mohamed M;Akbari M;Aquil S;Patel S;Al-Ogaili R;Whiteman M;Luke P;Sener A
通讯作者：
Sener A
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Friend, Peter J.
影响因子：
6
作者：
Bhattacharjee, Rabindra N.;Ruthirakanthan, Aushanth;Luke, Patrick P. W.
通讯作者：
Luke, Patrick P. W.
影响因子：
6.2
作者：
Kaths, J. Moritz;Echeverri, Juan;Selzner, Markus
通讯作者：
Selzner, Markus