Diaspirin Cross-Linked Hemoglobin and Blood Substitutes

Abstract

Oxygen delivery (DO 2 ) to organs and tissues depends on fl ow generated by the heart (cardiac output, CO) and arterial oxygen content. Arterial oxygen content depends on oxygen partial pressure (PaO 2 ) and hemoglobin (Hb) concentration and saturation. In case of hypoxemia and/or low CO states, Hb concentration may play a key role in preventing tissue hypoxia and cellular dysfunction.Although Hb concentration in perioperative settings and in critical care is a crucial aspect for almost all patients, the optimal values are still a matter of debate [ 1 ]. Nonetheless, current guidelines and recommendations suggest lower "transfusion triggers" than in the past, encouraging blood-saving techniques following a multidisciplinary, multi-procedural approach [ 2 ]. The diffi culties of supplying red blood cells (RBCs), the need to overcome problems of storage and transfusion (refrigeration and crossmatching), the aim to avoid potential transfusions' harming effects (infection, transfusion reactions, transfusion-related acute lung injury, immunomodulation) [ 3 , 4 ], and the need for alternatives to biological blood for religious reasons (e.g., Jehovah's Witnesses) [ 5 , 6 ] have led scientists and companies, over the past three decades, to synthesize and test artifi cial blood solutions. Oxygen carrier (OC) is a generic defi nition for blood substitutes, blood surrogates, artifi cial Hb, or artifi cial blood. These substances mimic oxygen-carrying function of the RBCs (Table 11.1 ) and are characterized by a long shelf life. In other words, OCs are pharmacological substances that aim to improve DO 2 independently from RBCs.

Oxygen Regulation in Development: Lessons from Embryogenesis towards Tissue Engineering

“…These adverse outcomes are largely a result of their high affinity for oxygen [Buehler et al, 2010], short half-life and their dissociation into dimers from tetramers [Bunn et al, 1969]. To improve half-life and stability of hemoglobin, strategies such as cross-linking [Hathazi et al, 2014; Romagnoli et al, 2015], polymerizing [Espes et al, 2015], coating with polydopamine [Wang et al, 2017], conjugating with dextran [Wang et al, 2017] and complexation with superoxide dismutase [Bian and Chang, 2015] have been studied. The underlying theme behind these strategies is to increase the size and reduce reactivity to diminish the toxicity and renal filtration.…”