Renal Protection Against Ischemia Reperfusion Injury: Hemoglobin-based Oxygen Carrier-201 Versus Blood as an Oxygen Carrier in Ex Vivo Subnormothermic Machine Perfusion

被引：50
作者：
Bhattacharjee, Rabindra N. [1 ,2 ,3 ]
Patel, Sanjay V. B. [4 ]
Sun, Qizhi [2 ,3 ]
Jiang, Larry [3 ]
Richard-Mohamed, Mahms [4 ]
Ruthirakanthan, Aushanth [3 ]
Aquil, Shahid [4 ]
Al-Ogaili, Rafid [4 ]
Juriasingani, Smriti [3 ]
Sener, Alp [1 ,2 ,3 ,4 ]
Luke, Patrick P. W. [1 ,2 ,3 ,4 ]
机构：
[1] Western Univ, Dept Surg, London, ON, Canada
[2] London Hlth Sci Ctr, Matthew Mailing Ctr Translat Transplantat Studies, London, ON, Canada
[3] Western Univ, Schulich Sch Med & Dent, Dept Surg, London, ON, Canada
[4] London Hlth Sci Ctr, Multi Organ Transplant Program, London, ON, Canada
来源：
TRANSPLANTATION | 2020年 / 104卷 / 03期
关键词：
COLD-STORAGE; ACUTE ANEMIA; PRESERVATION; DONATION; TRANSPLANTATION; SUBSTITUTES; OUTCOMES; KIDNEYS; MODEL;
D O I：
10.1097/TP.0000000000002967
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Background. The optimal method of oxygen delivery to donor kidneys during ex vivo machine perfusion has not been established. We have recently reported the beneficial effects of subnormothermic (22 degrees C) blood perfusion in the preservation of porcine donation after circulatory death kidneys. Since using blood as a clinical perfusate has limitations, including matching availability and potential presence of pathogen, we sought to assess hemoglobin-based oxygen carrier (HBOC-201) in oxygen delivery to the kidney for renal protection. Methods. Pig kidneys (n = 5) were procured after 30 minutes of warm in situ ischemia by cross-clamping the renal arteries. Organs were flushed with histidine tryptophan ketoglutarate solution and subjected to static cold storage or pulsatile perfusion with an RM3 pump at 22 degrees C for 4 hours with HBOC-201 and blood. Thereafter, kidneys were reperfused with normothermic (37 degrees C) oxygenated blood for 4 hours. Blood and urine were subjected to biochemical analysis. Total urine output, urinary protein, albumin/creatinine ratio, flow rate, resistance were measured. Acute tubular necrosis, apoptosis, urinary kidney damage markers, neutrophil gelatinase-associated lipocalin 1, and interleukin 6 were also assessed. Results. HBOC-201 achieved tissues oxygen saturation equivalent to blood. Furthermore, upon reperfusion, HBOC-201 treated kidneys had similar renal blood flow and function compared with blood-treated kidneys. Histologically, HBOC-201 and blood-perfused kidneys had vastly reduced acute tubular necrosis scores and degrees of terminal deoxynucleotidyl transferase 2'-deoxyuridine, 5'-triphosphate nick end labeling staining versus kidneys treated with cold storage. Urinary damage markers and IL6 levels were similarly reduced by both blood and HBOC-201. Conclusions. HBOC-201 is an excellent alternative to blood as an oxygen-carrying molecule in an ex vivo subnormothermic machine perfusion platform in kidneys.
引用
收藏
页码：482 / 489
页数：8
相关论文
共 24 条
  • [1] Aburawi MM, 2019, AM J TRANSPLANT
  • [2] Subnormothermic Oxygenated Perfusion Optimally Preserves Donor Kidneys Ex Vivo
    Bhattacharjee, Rabindra N.
    Ruthirakanthan, Aushanth
    Sun, Qizhi
    Richard-Mohamed, Mahms
    Luke, Sean
    Jiang, Larry
    Aquil, Shahid
    Sharma, Hemant
    Tun-Abraham, Mauro E.
    Alharbi, Bijad
    Haig, Aaron
    Sener, Alp
    Luke, Patrick P. W.
    [J]. KIDNEY INTERNATIONAL REPORTS, 2019, 4 (09): : 1323 - 1333
  • [3] CORM-401 Reduces Ischemia Reperfusion Injury in an Ex Vivo Renal Porcine Model of the Donation After Circulatory Death
    Bhattacharjee, Rabindra N.
    Richard-Mohamed, Mahms
    Sun, Qizhi
    Haig, Aaron
    Aboalsamh, Ghaleb
    Barrett, Peter
    Mayer, Richard
    Alhasan, Ibrahim
    Pineda-Solis, Karen
    Jiang, Larry
    Alharbi, Hajed
    Saha, Manujendra
    Patterson, Eric
    Sener, Alp
    Cepinskas, Gediminas
    Jevnikar, Anthony M.
    Luke, Patrick P. W.
    [J]. TRANSPLANTATION, 2018, 102 (07) : 1066 - 1074
  • [4] Management of acute anemia in a Jehovah's Witness patient with acute lymphoblastic leukemia with polymerized bovine hemoglobin-based oxygen carrier: a case report and review of literature
    Donahue, Laura L.
    Shapira, Iuliana
    Shander, Aryeh
    Kolitz, Jonathan
    Allen, Steven
    Greenburg, Gerson
    [J]. TRANSFUSION, 2010, 50 (07) : 1561 - 1567
  • [5] Liver Preservation With Machine Perfusion and a Newly Developed Cell-Free Oxygen Carrier Solution Under Subnormothermic Conditions
    Fontes, P.
    Lopez, R.
    van der Plaats, A.
    Vodovotz, Y.
    Minervini, M.
    Scott, V.
    Soltys, K.
    Shiva, S.
    Paranjpe, S.
    Sadowsky, D.
    Barclay, D.
    Zamora, R.
    Stolz, D.
    Demetris, A.
    Michalopoulos, G.
    Marsh, J. W.
    [J]. AMERICAN JOURNAL OF TRANSPLANTATION, 2015, 15 (02) : 381 - 394
  • [6] Normothermic Ex Vivo Kidney Perfusion Reduces Warm Ischemic Injury of Porcine Kidney Grafts Retrieved After Circulatory Death
    Hamar, Matyas
    Urbanellis, Peter
    Kaths, Moritz Johann
    Kollmann, Dagmar
    Linares, Ivan
    Ganesh, Sujani
    Wiebe, Aryn
    Cen, Jun Yu
    Yip, Paul
    John, Rohan
    Konvalinka, Ana
    Mucsi, Istvan
    Ghanekar, Anand
    Bagli, Darius
    Grant, David
    Robinson, Lisa A.
    Selzner, Markus
    [J]. TRANSPLANTATION, 2018, 102 (08) : 1262 - 1270
  • [7] Subnormothermic machine perfusion for preservation of porcine kidneys in a donation after circulatory death model
    Hoyer, Dieter P.
    Gallinat, Anja
    Swoboda, Sandra
    Wohlschlaeger, Jeremias
    Rauen, Ursula
    Paul, Andreas
    Minor, Thomas
    [J]. TRANSPLANT INTERNATIONAL, 2014, 27 (10) : 1097 - 1106
  • [8] Blood substitutes as pharmacotherapies in clinical practice
    Jahr, Jonathan S.
    Walker, Valeri
    Manoochehri, Katayoon
    [J]. CURRENT OPINION IN ANESTHESIOLOGY, 2007, 20 (04) : 325 - 330
  • [9] H2S supplementation: A novel method for successful organ preservation at subnormothermic temperatures
    Juriasingani, Smriti
    Akbari, Masoud
    Chan, Justin Y. H.
    Whiteman, Matthew
    Sener, Alp
    [J]. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, 2018, 81 : 57 - 66
  • [10] Normothermic Ex Vivo Kidney Perfusion Following Static Cold Storage-Brief, Intermediate, or Prolonged Perfusion for Optimal Renal Graft Reconditioning?
    Kaths, J. M.
    Echeverri, J.
    Linares, I.
    Cen, J. Y.
    Ganesh, S.
    Hamar, M.
    Urbanellis, P.
    Yip, P.
    John, R.
    Bagli, D.
    Mucsi, I.
    Ghanekar, A.
    Grant, D.
    Robinson, L. A.
    Selzner, M.
    [J]. AMERICAN JOURNAL OF TRANSPLANTATION, 2017, 17 (10) : 2580 - 2590
123