New Applications of HBOC-201: A 25-Year Review of the Literature

Cao, Min; Zhao, Yong; He, Hongli; Yue, Ruiming; Pan, Lingai; Hu, Huan; Ren, Yulan; Qin, Qin; Yi, Xueliang; Yin, Tao; Ma, Lina; Zhang, Dingding; Huang, Xiaobo

doi:10.3389/fmed.2021.794561

Cited by 18 publications

(17 citation statements)

References 113 publications

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“…Free serum hemoglobin was previously described as having adverse effects on kidneys, with extravasated hemoglobin causing nephrotoxicity and scavenging of nitric oxide (NO), thus leading to hypertension and higher intrarenal resistance [ 25 , 26 ]. The latter could also be observed in the HBOC groups in our study, while a possible obstruction of glomeruli could not be shown upon histological analysis.…”

Section: Discussionmentioning

confidence: 99%

HBOC-301 in Porcine Kidney Normothermic Machine Perfusion and the Effect of Vitamin C on Methemoglobin Formation

et al. 2022

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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®, 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.

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Section: Discussionmentioning

confidence: 99%

HBOC-301 in Porcine Kidney Normothermic Machine Perfusion and the Effect of Vitamin C on Methemoglobin Formation

et al. 2022

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“…36 Despite the failure of the HBOC products tested in the early 2000s, the search for a safe and efficacious HBOC is continuing today, 7,37 and newer applications are also being proposed. 3,8 Blood is a rare national resource. Its safety and availability are of vital concern.…”

Section: Discussionmentioning

confidence: 99%

“…6,7 Eight different hemoglobin preparations were developed and subjected to rigorous testing by commercial companies and the US Army, culminating in phase III clinical trials in which the safety and the ability of the product to effectively replace transfusion was tested. 8 Unfortunately, all the tested products failed to achieve FDA licensure because of both safety and efficacy concerns. 7,9 The reasons for the failure of the products are varied and may involve flaws in the products and in the execution of the trials.…”

Section: Background: Why Hboc's?mentioning

confidence: 99%

Digging Into Past HBOC Clinical Trials

Biro¹

2022

American Journal of Therapeutics

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The principal conclusion offered is that the BioPure product is safe for periodic replacement of transfusion, in total volumes up to 2500 mL with a caveat. HBOC treatment per se does not seem to contribute significantly to a cardiac adverse outcome "base," but the authors expressed concern about patients with cardiac disease and those older than 80 years. The product is a feasible "oxygen bridge to transfusion."Jahr Commentary

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“…Safety and efficacy of HBOCs was explored using numerous preclinical and clinical studies and a HBOCs product, HBOC-201 is approved for surgical patients with acute anemia and has been available in South Africa since 2001 [134]. However, a metaanalysis of cell-free hemoglobin-based blood substitutes concluded that the use of HBOCs was associated with a significantly increased risk of death and myocardial infarction based on an analysis of the available data from 13 randomized controlled trials [135]. After that the USFDA suspended all HBOC trials in the United States.…”

Section: Regulation Of Blood Pressure After Hemorrhagic Shockmentioning

confidence: 99%

“…After that the USFDA suspended all HBOC trials in the United States. Nonetheless, it was argued that if the risk of death due to low hemoglobin outweighed the risk of HBOCs, suspension on all HBOC trials could be fatal for these patients [135]. Subsequently, clinical trials for HBOCs are made available only through expanded access to save patients' lives when other interventions are not available.…”

Section: Regulation Of Blood Pressure After Hemorrhagic Shockmentioning

confidence: 99%

Controls of Central and Peripheral Blood Pressure and Hemorrhagic/Hypovolemic Shock

Ranjan¹,

Gulati²

2022

Preprint

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The pressure exerted on the heart and blood vessels because of blood flow is considered as an important parameter for the cardiovascular function. It determines sufficient blood perfusion as well as transportation of nutrition, oxygen and other essential factors to every organ. Pressure in the primary arteries located near the heart and the brain, known as central blood pressure (CBP), while in peripheral arteries, known as peripheral blood pressure (PBP). Normally, CBP and PBP are correlated; however, cardiovascular disorders interfere their regulation and affect the blood flow in vital organs and accessory organs, differently. Therefore, understanding each of them in normal and disease conditions is essential for managing various cardiovascular disorders and increasing their treatment outcomes. In this review, we have described the control systems (neural, hormonal, osmotic and cellular) of the blood pressure and its regulation in hypovolemic shock using centhaquine (Lyfaquin®) as a resuscitative agent.

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New Applications of HBOC-201: A 25-Year Review of the Literature

Cited by 18 publications

References 113 publications

HBOC-301 in Porcine Kidney Normothermic Machine Perfusion and the Effect of Vitamin C on Methemoglobin Formation

HBOC-301 in Porcine Kidney Normothermic Machine Perfusion and the Effect of Vitamin C on Methemoglobin Formation

Digging Into Past HBOC Clinical Trials

Controls of Central and Peripheral Blood Pressure and Hemorrhagic/Hypovolemic Shock

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