Haemoglobin-based oxygen carriers and myocardial infarction

Abstract

The incidence of investigator diagnosed myocardial infarction (MI) is greater in patients treated with haemoglobin-based oxygen carriers (HBOCs) than controls. Clinical trials and literature pertaining to possible HBOC toxicity mechanisms have been analyzed in order to identify possible reasons for this imbalance. MI diagnosis is hampered by potential interference of troponin assays by haemoglobin, haemolysis and bilirubin. Nevertheless, insofar as the reported incidence correlates with actual occurrence, there is a positive relationship between MI and HBOC dose and size. Preclinical and clinical data suggest that direct cardiac toxicity and coronary vasoconstriction are unlikely. More probable are detrimental intravascular interactions between HBOCs and components of the coagulation cascade, particularly dysfunctional endothelium. Elucidation of mechanisms is impeded by a lack of clinical data. Measurement of relevant biomarkers would be extremely useful in this regard and in improving patient selection criteria. Conduct of clinical trials in carefully selected patient populations after the development of improved protocols for MI diagnosis, along with concomitant biomarker data collection, is recommended.

Site-Specific Introduction of Negative Charges on the Protein Surface for Improving Global Functions of Recombinant Fetal Hemoglobin

“…In addition, these processes often generate heterogeneous products with mixed physiological behavior. Research on HBOCs has to date mainly focused on several properties of the Hb moiety, such as structural stability, oxidative reactivity, and nitrogen oxide scavenging, and several review papers have summarized the development and toxic issues of HBOCs (Alayash, 2017;Estep, 2019;Ferenz and Steinbicker, 2019). In this study, we have addressed an alternative strategy based on introducing negative charges on the surface of Hb.…”

Facing Trauma and Surgical Emergency in Space: Hemorrhagic Shock

“…New hemostats (nanotechnology) defined as self-assembling peptide nanofibers and chitosan nanofibers have also been used in clinical applications (Corwin et al, 2015;Chaturvedi et al, 2017;Chiara et al, 2018;Estep 2019;Huang et al, 2020;Tompeck et al, 2020).…”

“…Decreased diuresis in the initial phases of space flight is due to the increased retention after stress-mediated sympathetic activation Antonutto and di Prampero ( 2003 against transfusions or the need for a rare blood type. In addition, HBOCs may be used as an alternative to blood products in areas where the usual form of blood donation is not available, such as in space missions far from the Earth's orbit (Moore et al, 2009;Corwin et al, 2015;Weiskopf et al, 2017;Estep 2019;Nowak et al, 2019). Although HBOCs have many advantages as they can be stored at room temperature and require relatively little preparation, they are liquid and have a mass and volume similar to packed red blood cells.…”

ZIF-8 metal organic framework nanoparticle loaded with tense quaternary state polymerized bovine hemoglobin: potential red blood cell substitute with antioxidant properties

“…[5][6][7] Unfortunately, none of these commercial HBOCs received FDA approval for clinical use in the U.S. due to severe adverse events observed during Phase III clinical trials. 8,9 For instance, the presence of extracellular hemoglobin (Hb) and low molecular weight species (<300 kDa) in previous generations of HBOCs elicited vasoconstriction, systemic hypertension, 10,11 myocardial infarction, 12 acute renal damage, 13 and heart lesions. 13,14 This provides the rationale for the development of safer HBOCs.…”