MODIFIED HEMOGLOBIN-SOLUTIONS AS ARTIFICI AL 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 s tudy gives an overview of the development and present status of modifi ed Hb preparations. While human and bovine erythrocytes are used for p roduction on the one hand, human Hb variants can also be derived from yeast or bacteria as well as via transgenic animals through recombinan t DNA technology. The pronounced limitations of extraerythrocytic Hb, that is its high oxygen affinity and its inadequate intravascular pers istence, can be overcome by various modifications. Intravascular half- life of free Hb can be significantly increased by intramolecular stabi lization, linking to macromolecules, intermolecular cross-linking (Pol yHb solutions) or microencapsulation. Oxygen affinity of human Hb may be lowered by coupling of allosteric modulators to the 2,3-bisphosphog lycerate site, e.g. pyridoxal phosphate, whereas bovine Hb has an intr insically low oxygen affinity.Human pyridoxylated PolyHb solutions and bovine PolyHb solutions presently fulfill at least 2 of the 3 princip al requirements for an oxygen-transporting plasma substitute, i.e. mai ntenance of the circulating blood volume with provision of additionall y utilizable oxygen capacity Matters of concern with all Kb preparatio ns remain potential vasoconstrictive effects and renal toxicity. Major efforts being undertaken at present by industry and research groups g ive reason to hope, however, that the concept of modified Hb solutions as oxygen carriers will be realized in the foreseeable future.