Oxygen Delivery by Allosteric Effectors of Hemoglobin, Blood Substitutes, and Plasma Expanders

Abstract

The blood is a complex body fluid containing a large variety of cells and molecules serving vital functions. In particular, hemoglobin, contained in the red cells, loads, carries, and delivers oxygen and carbon dioxide in the circulation. In the last 30 years intense efforts have been made (1) to develop allosteric effectors of hemoglobin that affect oxygen affinity to treat diseases such as sickle‐cell anemia, ischemia, hypoxia, and to improve the efficiency of radio‐ and chemotherapy; (2) to obtain blood substitutes based either on organic molecules that solubilize oxygen or on genetically and/or chemically modified hemoglobins; and (3) to formulate solutions that maintain the blood volume and oncotic pressure in surgery and hemorrhagic events. In spite of the pharmacological relevance of these molecules, only plasma expanders are already available on the U.S. market. This is an indication of the difficulties in mimicking the multifaceted roles of hemoglobin.

PEGylation Promotes Hemoglobin Tetramer Dissociation

“…Hemoglobin-based oxygen carriers (HBOC) − are potential therapeutic agents for clinical needs that cannot be fullfilled by blood transfusions, such as (i) acute hemorrhages associated with accidents or weapon wounds in location far from hospitals, (ii) immunoreactivity against all red blood cell determinants, (iii) oxygen supply to patients that do not accept blood transfusions for religious dictates, (iv) oxygenation of ischemic tissues where red blood cells cannot diffuse , , and (v) increase in oxygen concentration in solid tumors for the improvement of radiation therapy , . Moreover, HBOCs can be used for (i) partial substitution of normal transfusion to save blood units during orthopedic surgeries, (ii) reduction of the exposure of preterm infants to adult red cells, potentially causing severe chronic pathologies, and (iii) safe supply of an oxygen supplier in world countries where blood units from healthy donors are limited.…”