[Modified hemoglobin solutions as artificial oxygen carriers].
At least theoretically, hemoglobin (Hb) solutions are ideal colloidal plasma substitutes because of their unique ability to take up oxygen, transport it in bound form, and release it peripherally. The present study gives an overview of the development and present status of modified Hb preparations. While human and bovine erythrocytes are used for production on the one hand, human Hb variants can also be derived from yeast or bacteria as well as via transgenic animals through recombinant DNA technology. The pronounced limitations of extraerythrocytic Hb, that is its high oxygen affinity and its inadequate intravascular persistence, can be overcome by various modifications. Intravascular half-life of free Hb can be significantly increased by intramolecular stabilization, linking to macromolecules, intermolecular cross-linking (PolyHb solutions) or microencapsulation. Oxygen affinity of human Hb may be lowered by coupling of allosteric modulators to the 2,3-bisphosphoglycerate site, e.g. pyridoxal phosphate, whereas bovine Hb has an intrinsically low oxygen affinity. Human pyridoxylated PolyHb solutions and bovine PolyHb solutions presently fulfill at least 2 of the 3 principal requirements for an oxygen-transporting plasma substitute, i.e. maintenance of the circulating blood volume with provision of additionally utilizable oxygen capacity. Matters of concern with all Hb preparations remain potential vasoconstrictive effects and renal toxicity. Major efforts being undertaken at present by industry and research groups give reason to hope, however, that the concept of modified Hb solutions as oxygen carriers will be realized in the foreseeable future.
Abteilung Anaesthesiologie, Universität Tübingen.
G
G
Lenz
U
U
Bissinger
D000818:Animals; D001802:Blood Substitutes; D002417:Cattle; D006454:Hemoglobins; D006801:Humans; D010100:Oxygen / Q000097:blood*; D011994:Recombinant Proteins
D001802:Blood Substitutes; D006454:Hemoglobins; D011994:Recombinant Proteins; C037158:polyhemoglobin; D010100:Oxygen
Modifizierte Hämoglobinlösungen als künstliche Sauerstoffträger.