Thomas Agius, Julien Songeon, Arnaud Lyon, Justine Longchamp, Raphael Ruttimann, Florent Allagnat, Sébastien Déglise, Jean-Marc Corpataux, Déla Golshayan, Léo Buhler, Raphael Meier, Heidi Yeh, James F Markmann, Korkut Uygun, Christian Toso, Antoine Klauser, Francois Lazeyras, Alban Longchamp
{"title":"猪肾体外灌注和移植过程中的硫化钠治疗。","authors":"Thomas Agius, Julien Songeon, Arnaud Lyon, Justine Longchamp, Raphael Ruttimann, Florent Allagnat, Sébastien Déglise, Jean-Marc Corpataux, Déla Golshayan, Léo Buhler, Raphael Meier, Heidi Yeh, James F Markmann, Korkut Uygun, Christian Toso, Antoine Klauser, Francois Lazeyras, Alban Longchamp","doi":"10.1097/TXD.0000000000001508","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>In rodents, hydrogen sulfide (H<sub>2</sub>S) reduces ischemia-reperfusion injury and improves renal graft function after transplantation. Here, we hypothesized that the benefits of H<sub>2</sub>S are conserved in pigs, a more clinically relevant model.</p><p><strong>Methods: </strong>Adult porcine kidneys retrieved immediately or after 60 min of warm ischemia (WI) were exposed to 100 µM sodium hydrosulfide (NaHS) (1) during the hypothermic ex vivo perfusion only, (2) during WI only, and (3) during both WI and ex vivo perfusion. Kidney perfusion was evaluated with dynamic contrast-enhanced MRI. MRI spectroscopy was further employed to assess energy metabolites including ATP. Renal biopsies were collected at various time points for histopathological analysis.</p><p><strong>Results: </strong>Perfusion for 4 h pig kidneys with Belzer MPS UW + NaHS resulted in similar renal perfusion and ATP levels than perfusion with UW alone. Similarly, no difference was observed when NaHS was administered in the renal artery before ischemia. After autotransplantation, no improvement in histologic lesions or cortical/medullary kidney perfusion was observed upon H<sub>2</sub>S administration. In addition, AMP and ATP levels were identical in both groups.</p><p><strong>Conclusions: </strong>In conclusion, treatment of porcine kidney grafts using NaHS did not result in a significant reduction of ischemia-reperfusion injury or improvement of kidney metabolism. Future studies will need to define the benefits of H<sub>2</sub>S in human, possibly using other molecules as H<sub>2</sub>S donors.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":"9 11","pages":"e1508"},"PeriodicalIF":1.9000,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617874/pdf/","citationCount":"0","resultStr":"{\"title\":\"Sodium Hydrosulfide Treatment During Porcine Kidney Ex Vivo Perfusion and Transplantation.\",\"authors\":\"Thomas Agius, Julien Songeon, Arnaud Lyon, Justine Longchamp, Raphael Ruttimann, Florent Allagnat, Sébastien Déglise, Jean-Marc Corpataux, Déla Golshayan, Léo Buhler, Raphael Meier, Heidi Yeh, James F Markmann, Korkut Uygun, Christian Toso, Antoine Klauser, Francois Lazeyras, Alban Longchamp\",\"doi\":\"10.1097/TXD.0000000000001508\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>In rodents, hydrogen sulfide (H<sub>2</sub>S) reduces ischemia-reperfusion injury and improves renal graft function after transplantation. Here, we hypothesized that the benefits of H<sub>2</sub>S are conserved in pigs, a more clinically relevant model.</p><p><strong>Methods: </strong>Adult porcine kidneys retrieved immediately or after 60 min of warm ischemia (WI) were exposed to 100 µM sodium hydrosulfide (NaHS) (1) during the hypothermic ex vivo perfusion only, (2) during WI only, and (3) during both WI and ex vivo perfusion. Kidney perfusion was evaluated with dynamic contrast-enhanced MRI. MRI spectroscopy was further employed to assess energy metabolites including ATP. Renal biopsies were collected at various time points for histopathological analysis.</p><p><strong>Results: </strong>Perfusion for 4 h pig kidneys with Belzer MPS UW + NaHS resulted in similar renal perfusion and ATP levels than perfusion with UW alone. Similarly, no difference was observed when NaHS was administered in the renal artery before ischemia. After autotransplantation, no improvement in histologic lesions or cortical/medullary kidney perfusion was observed upon H<sub>2</sub>S administration. In addition, AMP and ATP levels were identical in both groups.</p><p><strong>Conclusions: </strong>In conclusion, treatment of porcine kidney grafts using NaHS did not result in a significant reduction of ischemia-reperfusion injury or improvement of kidney metabolism. Future studies will need to define the benefits of H<sub>2</sub>S in human, possibly using other molecules as H<sub>2</sub>S donors.</p>\",\"PeriodicalId\":23225,\"journal\":{\"name\":\"Transplantation Direct\",\"volume\":\"9 11\",\"pages\":\"e1508\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2023-10-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617874/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Transplantation Direct\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1097/TXD.0000000000001508\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/11/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"TRANSPLANTATION\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transplantation Direct","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1097/TXD.0000000000001508","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/11/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"TRANSPLANTATION","Score":null,"Total":0}
Sodium Hydrosulfide Treatment During Porcine Kidney Ex Vivo Perfusion and Transplantation.
Background: In rodents, hydrogen sulfide (H2S) reduces ischemia-reperfusion injury and improves renal graft function after transplantation. Here, we hypothesized that the benefits of H2S are conserved in pigs, a more clinically relevant model.
Methods: Adult porcine kidneys retrieved immediately or after 60 min of warm ischemia (WI) were exposed to 100 µM sodium hydrosulfide (NaHS) (1) during the hypothermic ex vivo perfusion only, (2) during WI only, and (3) during both WI and ex vivo perfusion. Kidney perfusion was evaluated with dynamic contrast-enhanced MRI. MRI spectroscopy was further employed to assess energy metabolites including ATP. Renal biopsies were collected at various time points for histopathological analysis.
Results: Perfusion for 4 h pig kidneys with Belzer MPS UW + NaHS resulted in similar renal perfusion and ATP levels than perfusion with UW alone. Similarly, no difference was observed when NaHS was administered in the renal artery before ischemia. After autotransplantation, no improvement in histologic lesions or cortical/medullary kidney perfusion was observed upon H2S administration. In addition, AMP and ATP levels were identical in both groups.
Conclusions: In conclusion, treatment of porcine kidney grafts using NaHS did not result in a significant reduction of ischemia-reperfusion injury or improvement of kidney metabolism. Future studies will need to define the benefits of H2S in human, possibly using other molecules as H2S donors.
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