Artificial blood: where are we now?

Abstract

Background. The creation of artificial blood (AB) and/or its components can change medicine, but currently available artificial oxygen carriers (AOC) do not perform other blood functions: vascular volume maintenance, coagulation, immunity, transport of neurotransmitters, nutrients and waste. Objective. To describe the current situation regarding AB. Materials and methods. Analysis of literature data on this issue. Results and discussion. The need to create an AB is justified by the high cost of collecting, processing and storing donor blood, low infectious safety of drugs received against HIV, viral hepatitis B and C, cytomegalovirus, etc., reduction of the number of donors, problems with blood incompatibility. Immunological effects of blood transfusions are associated with a higher frequency of infectious processes during surgery, slowing of wound healing and progression of malignant diseases. Requirements for an ideal AB preparation include adequate oxygen uptake and delivery under physiological conditions, no toxic or physiological effects, ability to be eliminated and excreted by the human body, sufficient intravascular half-life, ease of use and storage, stability at room temperature, universal compatibility, availability and low cost, ability to maintain blood pressure and pH, viscosity similar to real blood. Available AOC include oxygen-transport solutions based on hemoglobin and perfluorocarbon compounds (PFC) in the form of emulsions. Natural (human, bovine) or genetically modified hemoglobin is used for the production of the former, and hemoglobin of yeast or bacterial origin can also be used. The advantages of hemoglobin solutions include the increased erythropoietin production, adequate oxygen delivery at a hemoglobin level of 20 g/L without side effects, complete absence of virus transmission and 25 % better reperfusion recovery than with real blood. Potential fields of AOC use include shock, organ ischemia, erythrocyte incompatibility, acute lung injury, organ storage for transplantation, cardioplegia, sickle cell anemia, tumor treatment, and air embolism. The main problem is the release of pro-inflammatory cytokines in response to hemoglobin solution administration. Side effects of these solutions include neuro- and nephrotoxicity, immunosuppression, vasoconstriction, coagulopathy, release of free radicals, and errors in blood tests. In turn, PFC does not bind oxygen, but dissolves it in proportion to the partial pressure. PFC are eliminated by phagocytes and eventually excreted by the lungs during respiration. PFC particles are much smaller than natural erythrocytes (0.2 vs. 7 μm) and are easier to deform, which facilitates their delivery to ischemic areas. Side effects of PFC include transient face flushing, headache and back pain, nausea, fever, anaphylactoid reactions, bleeding tendency, pulmonary edema, and acute right ventricular failure. Because high partial pressures are required to achieve the desired PFC effects, artificial lung ventilation may be required. In addition to hemoglobin-based AOC and PFC, hemoglobin in liposomal erythrocyte form, hemoglobin in nanocapsules, nanoarchitectonic complexes of hemoglobin are under development. Conclusions. 1. The creation of AB may revolutionize medicine. 2. The need to create an AB is justified by the high cost of collection, processing and storage of donor blood, its low infectious safety, reduction of the number of donors, problems due to blood incompatibility. 3. AOC include hemoglobin-based oxygen-transporting solutions and PFC emulsions. 4. Further studies are needed to improve existing AB preparations and create new ones.