Evaluating the Effects of Subnormothermic Perfusion with AP39 in a Novel Blood-Free Model of Ex Vivo Kidney Preservation and Reperfusion
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/13/7180 |
| _version_ | 1797528018565988352 |
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| author | Smriti Juriasingani Ashley Jackson Max Yulin Zhang Aushanth Ruthirakanthan George J. Dugbartey Emrullah Sogutdelen Max Levine Moaath Mandurah Matthew Whiteman Patrick Luke Alp Sener |
| author_facet | Smriti Juriasingani Ashley Jackson Max Yulin Zhang Aushanth Ruthirakanthan George J. Dugbartey Emrullah Sogutdelen Max Levine Moaath Mandurah Matthew Whiteman Patrick Luke Alp Sener |
| author_sort | Smriti Juriasingani |
| collection | DOAJ |
| description | 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<sub>2</sub> 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. |
| first_indexed | 2024-03-10T09:52:09Z |
| format | Article |
| id | doaj.art-c9ed6530a9ff4d48a61f71e9c4b83d66 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:52:09Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c9ed6530a9ff4d48a61f71e9c4b83d662023-11-22T02:41:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012213718010.3390/ijms22137180Evaluating the Effects of Subnormothermic Perfusion with AP39 in a Novel Blood-Free Model of Ex Vivo Kidney Preservation and ReperfusionSmriti Juriasingani0Ashley Jackson1Max Yulin Zhang2Aushanth Ruthirakanthan3George J. Dugbartey4Emrullah Sogutdelen5Max Levine6Moaath Mandurah7Matthew Whiteman8Patrick Luke9Alp Sener10Department of Microbiology and Immunology, Western University, London, ON N6A 5C1, CanadaMatthew Mailing Center for Translational Transplant Studies, London Health Sciences Centre, London, ON N6A 5A5, CanadaDepartment of Microbiology and Immunology, Western University, London, ON N6A 5C1, CanadaMatthew Mailing Center for Translational Transplant Studies, London Health Sciences Centre, London, ON N6A 5A5, CanadaMatthew Mailing Center for Translational Transplant Studies, London Health Sciences Centre, London, ON N6A 5A5, CanadaDepartment of Urology, Bolu Abant Izzet Baysal University, Bolu 14030, TurkeyMatthew Mailing Center for Translational Transplant Studies, London Health Sciences Centre, London, ON N6A 5A5, CanadaMatthew Mailing Center for Translational Transplant Studies, London Health Sciences Centre, London, ON N6A 5A5, CanadaSt. Luke’s Campus, University of Exeter Medical School, Exeter EX1 2HZ, UKMatthew Mailing Center for Translational Transplant Studies, London Health Sciences Centre, London, ON N6A 5A5, CanadaDepartment of Microbiology and Immunology, Western University, London, ON N6A 5C1, CanadaThe 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<sub>2</sub> 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.https://www.mdpi.com/1422-0067/22/13/7180kidney preservationkidney transplantationhydrogen sulfide (H<sub>2</sub>S)AP39donation after cardiac death (DCD)subnormothermic |
| spellingShingle | Smriti Juriasingani Ashley Jackson Max Yulin Zhang Aushanth Ruthirakanthan George J. Dugbartey Emrullah Sogutdelen Max Levine Moaath Mandurah Matthew Whiteman Patrick Luke Alp Sener Evaluating the Effects of Subnormothermic Perfusion with AP39 in a Novel Blood-Free Model of Ex Vivo Kidney Preservation and Reperfusion International Journal of Molecular Sciences kidney preservation kidney transplantation hydrogen sulfide (H<sub>2</sub>S) AP39 donation after cardiac death (DCD) subnormothermic |
| title | Evaluating the Effects of Subnormothermic Perfusion with AP39 in a Novel Blood-Free Model of Ex Vivo Kidney Preservation and Reperfusion |
| title_full | Evaluating the Effects of Subnormothermic Perfusion with AP39 in a Novel Blood-Free Model of Ex Vivo Kidney Preservation and Reperfusion |
| title_fullStr | Evaluating the Effects of Subnormothermic Perfusion with AP39 in a Novel Blood-Free Model of Ex Vivo Kidney Preservation and Reperfusion |
| title_full_unstemmed | Evaluating the Effects of Subnormothermic Perfusion with AP39 in a Novel Blood-Free Model of Ex Vivo Kidney Preservation and Reperfusion |
| title_short | Evaluating the Effects of Subnormothermic Perfusion with AP39 in a Novel Blood-Free Model of Ex Vivo Kidney Preservation and Reperfusion |
| title_sort | evaluating the effects of subnormothermic perfusion with ap39 in a novel blood free model of ex vivo kidney preservation and reperfusion |
| topic | kidney preservation kidney transplantation hydrogen sulfide (H<sub>2</sub>S) AP39 donation after cardiac death (DCD) subnormothermic |
| url | https://www.mdpi.com/1422-0067/22/13/7180 |
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