Hemoglobin substitutes

Anbari, Kevin K.; Garino, Jonathan P.; Mackenzie, Colin F.

doi:10.1007/s00586-004-0737-x

Cited by 20 publications

(11 citation statements)

References 22 publications

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“…(12) Because of the extraction and purification process, potential contaminants including plasma proteins, endotoxins, bacteria, viruses, and the prions responsible for bovine spongiform encephalopathy and variant Creutzfeld-Jakob disease are removed, resulting in a sterile, pyrogen-free solution. (13) The in vivo half-life of HBOC-201 is approximately 20 hours. (13) A downside to the use of HBOC-201 is the potential formation of methemoglobin (metHb).…”

Section: Oxygen Carrier Hboc-201mentioning

confidence: 99%

“…(13) The in vivo half-life of HBOC-201 is approximately 20 hours. (13) A downside to the use of HBOC-201 is the potential formation of methemoglobin (metHb). However, the small amount of HBOC-201 that would reach the recipient in a transplantation setting is minimal as the perfusion solution would be washed out prior to transplantation.…”

Section: Oxygen Carrier Hboc-201mentioning

confidence: 99%

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Normothermic machine perfusion of donor livers without the need for human blood products

et al. 2018

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Normothermic machine perfusion (NMP) enables viability assessment of donor livers prior to transplantation. NMP is frequently performed by using human blood products including red blood cells (RBCs) and fresh frozen plasma (FFP). Our aim was to examine the efficacy of a novel machine perfusion solution based on polymerized bovine hemoglobin‐based oxygen carrier (HBOC)‐201. Twenty‐four livers declined for transplantation were transported by using static cold storage. Upon arrival, livers underwent NMP for 6 hours using pressure‐controlled portal and arterial perfusion. A total of 12 livers were perfused using a solution based on RBCs and FFPs (historical cohort), 6 livers with HBOC‐201 and FFPs, and another 6 livers with HBOC‐201 and gelofusine, a gelatin‐based colloid solution. Compared with RBC + FFP perfused livers, livers perfused with HBOC‐201 had significantly higher hepatic adenosine triphosphate content, cumulative bile production, and portal and arterial flows. Biliary secretion of bicarbonate, bilirubin, bile salts, and phospholipids was similar in all 3 groups. The alanine aminotransferase concentration in perfusate was lower in the HBOC‐201–perfused groups. In conclusion, NMP of human donor livers can be performed effectively using HBOC‐201 and gelofusine, eliminating the need for human blood products. Perfusing livers with HBOC‐201 is at least similar to perfusion with RBCs and FFP. Some of the biomarkers of liver function and injury even suggest a possible superiority of an HBOC‐201–based perfusion solution and opens a perspective for further optimization of machine perfusion techniques. Liver Transplantation 24 528–538 2018 AASLD.

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Section: Oxygen Carrier Hboc-201mentioning

confidence: 99%

Section: Oxygen Carrier Hboc-201mentioning

confidence: 99%

Normothermic machine perfusion of donor livers without the need for human blood products

et al. 2018

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“…Hemoglobin-based oxygen carriers (HBOC) have been the most extensively studied and tested in preclinical and clinical trials that have shown success in diminishing the number of blood transfusions as well as an overall favorable side-effect profile (7). Recent investigations have shown that HBOC are not only simple red blood cell transfusion substitutes but effective oxygen donators in terms of tissue oxygenation (8,9).…”

Section: Introductionmentioning

confidence: 99%

Immune Effects of Resuscitation With Hboc-201, a Hemoglobin-Based Oxygen Carrier, in Swine With Moderately Severe Hemorrhagic Shock From Controlled Hemorrhage

Dong¹,

Hall²,

Golech³

et al. 2006

Shock

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HBOC-201, a hemoglobin-based oxygen carrier, improved physiologic parameters and survival in hemorrhagic shock (HS) animal models. However, resuscitation from HS and the properties of different fluids influence immune responses. The aim of this study was to determine if HBOC-201 significantly alters immune function in traumatic HS. Anesthetized pigs underwent soft tissue injury, controlled hemorrhage of 40% of blood volume, and resuscitation with HBOC-201 or Hextend, or no resuscitation. Sequential whole-blood samples were collected for analyses of leukocyte differential (hematology analyzer), T-lymphocyte subsets (CD3, CD4, and CD8) (FACS), lymphocyte adhesion marker CD49d (alpha4-integrin) expression (FACS), plasma cytokines-tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10-(ELISA), and lymphocyte apoptosis (annexin-V/propidium iodide staining) (FACS). Statistical analyses were performed by the mixed procedure. Total WBC counts decreased posthemorrhage in both resuscitation groups. Lymphocyte percentages decreased and PMN percentages increased around 4 h posthemorrhage in all groups. CD3 cells decreased in all groups, but CD4 and CD8 cells decreased only in the resuscitation groups. TNF-alpha levels were not detectable in any groups. IL-6 levels were similar across treatment groups (P > 0.05); however, IL-10 levels were higher in the HBOC group, as early as 1 h posthemorrhage (P = 0.04). Increases in lymphocytic CD49d expression levels and apoptosis occurred only in nonresuscitation and Hextend groups, respectively (P < or = 0.01). In comparison with Hextend, HBOC-201 had no significant adverse or beneficial effects on immune function in this model of moderately severe HS in swine, suggesting that it may be safe as a resuscitation fluid in HS patients.

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“…PRBC. However, the amount of HBOC reaching the recipient circulation in a clinical setting would be negligible, because the perfusion solution would be washed out prior to transplantation 26,27,38,39. Histology reveals glomerular tufts irregularly engorged with accumulated luminal red blood cells (black arrows), loss of the epithelial brush border, frequent cytoplasmic vacuolations (blue arrows), and rupture of some tubules with interstitial edema (red arrows).…”

mentioning

confidence: 99%

Synthetic hemoglobin-based oxygen carriers are an acceptable alternative for packed red blood cells in normothermic kidney perfusion

Aburawi

Fontan

Karimian

et al. 2019

American Journal of Transplantation

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contributed equally to this work.Abbreviations: ADP, adenosine diphosphate; AMP, adenosine monophosphate; ATP, adenosine triphosphate; CIT, cold ischemia time; DBD, donation after brain death; DCD, donation after circulatory death; FENa, fractional excretion of sodium; HBOC, hemoglobin-based oxygen carrier; HMP, hypothermic machine perfusion; NEDS, New England Donor Services; NEVKP, normothermic ex vivo kidney perfusion; NMP, normothermic machine perfusion; PRBC, packed red blood cells; QAS, quality assessment score; SCS, static cold storage; WIT, warm ischemia time.Normothermic machine perfusion presents a novel platform for pretransplant assessment and reconditioning of kidney grafts. Maintaining the metabolic activity of a preserved graft at physiologic levels requires an adequate oxygen supply, typically delivered by crystalloid solutions supplemented with red blood cells. In this study, we explored the feasibility of using a synthetic hemoglobin-based oxygen carrier (HBOC) in human kidney normothermic perfusion. Fourteen discarded human kidneys were perfused for 6 hours at a mean temperature of 37°C using a pressurecontrolled system. Kidneys were perfused with a perfusion solution supplemented with either HBOC (n = 7) or packed red blood cells (PRBC) (n = 7) to increase oxygencarrying capacity. Renal artery resistance, oxygen extraction, metabolic activity, energy stores, and histological features were evaluated. Throughout perfusion, kidneys from both groups exhibited comparable behavior regarding vascular flow (P = .66), oxygen consumption (P = .88), and reconstitution of tissue adenosine triphosphate (P = .057). Lactic acid levels were significantly higher in kidneys perfused with PRBC (P = .007). Histological findings were comparable between groups, and there was no evidence of histological damage caused by the HBOC. This feasibility experiment demonstrates that a HBOC solution can offer a logistically more convenient off-theshelf alternative to PRBC in normothermic machine perfusion of human kidneys. K E Y W O R D Sbasic (laboratory) research/science, kidney transplantation/nephrology, organ perfusion and preservation, organ procurement and allocation, tissue/organ engineering, translational research/science | 2815 ABURAWI et Al.

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Hemoglobin substitutes

Cited by 20 publications

References 22 publications

Normothermic machine perfusion of donor livers without the need for human blood products

Normothermic machine perfusion of donor livers without the need for human blood products

Immune Effects of Resuscitation With Hboc-201, a Hemoglobin-Based Oxygen Carrier, in Swine With Moderately Severe Hemorrhagic Shock From Controlled Hemorrhage

Synthetic hemoglobin-based oxygen carriers are an acceptable alternative for packed red blood cells in normothermic kidney perfusion

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