HBOC-301 in Porcine Kidney Normothermic Machine Perfusion and the Effect of Vitamin C on Methemoglobin Formation
Normothermic machine perfusion (NMP) of kidneys in combination with an optimized perfusate composition may increase donor organ preservation quality, especially in the case of marginal donor grafts. Optimization of currently employed perfusates is still a subject of present research. Due to the adva...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/7/1329 |
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| author | Eileen Edgworth Lisa Ernst Zoltan Czigany Turgay Saritas Laura Sophie Zarnitz Marc Wiartalla Peter Boor Eva Miriam Buhl Rolf Rossaint René H. Tolba Benedict Doorschodt Gregor Fabry Christian Bleilevens |
| author_facet | Eileen Edgworth Lisa Ernst Zoltan Czigany Turgay Saritas Laura Sophie Zarnitz Marc Wiartalla Peter Boor Eva Miriam Buhl Rolf Rossaint René H. Tolba Benedict Doorschodt Gregor Fabry Christian Bleilevens |
| author_sort | Eileen Edgworth |
| collection | DOAJ |
| description | Normothermic machine perfusion (NMP) of kidneys in combination with an optimized perfusate composition may increase donor organ preservation quality, especially in the case of marginal donor grafts. Optimization of currently employed perfusates is still a subject of present research. Due to the advantages of being cell-free, easy to store, and having minimal antigenicity, hemoglobin-based oxygen carriers, such as HBOC-301 (Oxyglobin<sup>®</sup>, Hemoglobin Oxygen Therapeutics LLC, Souderton, PA, USA), offer an alternative to the commonly used perfusates based on packed red blood cells (pRBC). As previously described, using HBOC results in formation of methemoglobin (metHb) as an adverse effect, inducing hypoxic conditions during the perfusion. As a potential counterpart to metHb formation, the application of the antioxidant ascorbic acid (VitC) is of high interest. Therefore, this study was conducted in four experimental groups, to compare the effect of NMP with (1) HBOC or (3) pRBC, and additionally examine a beneficial effect of VitC in both groups (2) HBOC + VitC and (4) pRBC + VitC. All groups were subjected to NMP for 6 h at a pressure of 75 mmHg. Kidneys in the HBOC groups had a significantly lower renal blood flow and increasing intrarenal resistance, with reduced renal function in comparison to the pRBC groups, as demonstrated by significantly lower creatinine clearance and higher fractional sodium excretion rates. Clinical chemistry markers for tissue damage (LDH, lactate) were higher in the HBOC groups, whereas no significant histological differences were observed. Although the application of VitC decreased oxidative stress levels, it was not able to significantly increase the outcome parameters mentioned above in either group. This study demonstrated that HBOC-301 is inferior to pRBCs in our porcine kidney NMP model, independent of additional VitC administration. Oxidative stress and fragmentation of the hemoglobin polymers could be detected as a possible reason for these results, hence further research, focusing on the use of cell-free oxygen carriers that do not exhibit this complex of issues, is required. |
| first_indexed | 2024-03-09T10:23:08Z |
| format | Article |
| id | doaj.art-529ba1421c7c40308c80a77c4dfd6ced |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T10:23:08Z |
| publishDate | 2022-07-01 |
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| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-529ba1421c7c40308c80a77c4dfd6ced2023-12-01T21:49:54ZengMDPI AGAntioxidants2076-39212022-07-01117132910.3390/antiox11071329HBOC-301 in Porcine Kidney Normothermic Machine Perfusion and the Effect of Vitamin C on Methemoglobin FormationEileen Edgworth0Lisa Ernst1Zoltan Czigany2Turgay Saritas3Laura Sophie Zarnitz4Marc Wiartalla5Peter Boor6Eva Miriam Buhl7Rolf Rossaint8René H. Tolba9Benedict Doorschodt10Gregor Fabry11Christian Bleilevens12Department of Anesthesiology, Medical Faculty, University Hospital RWTH Aachen, 52074 Aachen, GermanyInstitute for Laboratory Animal Science and Experimental Surgery, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, GermanyDepartment of Surgery and Transplantation, University Hospital RWTH Aachen, 52074 Aachen, GermanyDivision of Nephrology and Immunology, University Hospital RWTH Aachen, 52074 Aachen, GermanyDepartment of Anesthesiology, Medical Faculty, University Hospital RWTH Aachen, 52074 Aachen, GermanyInstitute of Computer Sciences 11, RWTH Aachen University, 52074 Aachen, GermanyInstitute of Pathology, Division of Nephrology, Medical Faculty, RWTH Aachen, 52074 Aachen, GermanyInstitute of Pathology, Division of Nephrology, Medical Faculty, RWTH Aachen, 52074 Aachen, GermanyDepartment of Anesthesiology, Medical Faculty, University Hospital RWTH Aachen, 52074 Aachen, GermanyInstitute for Laboratory Animal Science and Experimental Surgery, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, GermanyInstitute for Laboratory Animal Science and Experimental Surgery, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, GermanyDepartment of Anesthesiology, Medical Faculty, University Hospital RWTH Aachen, 52074 Aachen, GermanyDepartment of Anesthesiology, Medical Faculty, University Hospital RWTH Aachen, 52074 Aachen, GermanyNormothermic machine perfusion (NMP) of kidneys in combination with an optimized perfusate composition may increase donor organ preservation quality, especially in the case of marginal donor grafts. Optimization of currently employed perfusates is still a subject of present research. Due to the advantages of being cell-free, easy to store, and having minimal antigenicity, hemoglobin-based oxygen carriers, such as HBOC-301 (Oxyglobin<sup>®</sup>, Hemoglobin Oxygen Therapeutics LLC, Souderton, PA, USA), offer an alternative to the commonly used perfusates based on packed red blood cells (pRBC). As previously described, using HBOC results in formation of methemoglobin (metHb) as an adverse effect, inducing hypoxic conditions during the perfusion. As a potential counterpart to metHb formation, the application of the antioxidant ascorbic acid (VitC) is of high interest. Therefore, this study was conducted in four experimental groups, to compare the effect of NMP with (1) HBOC or (3) pRBC, and additionally examine a beneficial effect of VitC in both groups (2) HBOC + VitC and (4) pRBC + VitC. All groups were subjected to NMP for 6 h at a pressure of 75 mmHg. Kidneys in the HBOC groups had a significantly lower renal blood flow and increasing intrarenal resistance, with reduced renal function in comparison to the pRBC groups, as demonstrated by significantly lower creatinine clearance and higher fractional sodium excretion rates. Clinical chemistry markers for tissue damage (LDH, lactate) were higher in the HBOC groups, whereas no significant histological differences were observed. Although the application of VitC decreased oxidative stress levels, it was not able to significantly increase the outcome parameters mentioned above in either group. This study demonstrated that HBOC-301 is inferior to pRBCs in our porcine kidney NMP model, independent of additional VitC administration. Oxidative stress and fragmentation of the hemoglobin polymers could be detected as a possible reason for these results, hence further research, focusing on the use of cell-free oxygen carriers that do not exhibit this complex of issues, is required.https://www.mdpi.com/2076-3921/11/7/1329normothermic machine perfusionkidney preservationkidney transplantationischemia reperfusion injuryhemoglobin-based oxygen carrier |
| spellingShingle | Eileen Edgworth Lisa Ernst Zoltan Czigany Turgay Saritas Laura Sophie Zarnitz Marc Wiartalla Peter Boor Eva Miriam Buhl Rolf Rossaint René H. Tolba Benedict Doorschodt Gregor Fabry Christian Bleilevens HBOC-301 in Porcine Kidney Normothermic Machine Perfusion and the Effect of Vitamin C on Methemoglobin Formation Antioxidants normothermic machine perfusion kidney preservation kidney transplantation ischemia reperfusion injury hemoglobin-based oxygen carrier |
| title | HBOC-301 in Porcine Kidney Normothermic Machine Perfusion and the Effect of Vitamin C on Methemoglobin Formation |
| title_full | HBOC-301 in Porcine Kidney Normothermic Machine Perfusion and the Effect of Vitamin C on Methemoglobin Formation |
| title_fullStr | HBOC-301 in Porcine Kidney Normothermic Machine Perfusion and the Effect of Vitamin C on Methemoglobin Formation |
| title_full_unstemmed | HBOC-301 in Porcine Kidney Normothermic Machine Perfusion and the Effect of Vitamin C on Methemoglobin Formation |
| title_short | HBOC-301 in Porcine Kidney Normothermic Machine Perfusion and the Effect of Vitamin C on Methemoglobin Formation |
| title_sort | hboc 301 in porcine kidney normothermic machine perfusion and the effect of vitamin c on methemoglobin formation |
| topic | normothermic machine perfusion kidney preservation kidney transplantation ischemia reperfusion injury hemoglobin-based oxygen carrier |
| url | https://www.mdpi.com/2076-3921/11/7/1329 |
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