The development of haemoglobin preparations for various indications.

The investigational concepts and experimental results of several research groups cooperating on haemoglobin solutions are reviewed over a ten years' period of time. Starting with solutions of stroma-cleared, nearly unaltered human erythrocyte haemoglobin they recognized the disadvantages of a high oxygen affinity, on one hand, and a short intravascular half-life on the other. The former drawback was first compensated by attempts to raise the 2,3-diphospho-glycerate level (Hb-DPG). Later on, better results were achieved by chemical modification of the free haemoglobin with pyrodixal-phospate. This type of pyridoxal-phosphate modified haemoglobin (HbPP) gained particular interest for myocardial perfusion. In order to prolong the intravascular efficiency of preparations to be infused into the central circulation, the pyridoxal-phosphate modified haemoglobin molecules were increased in size by intermolecular cross-linkage (HbHbPP). Possible clinical applications are argued of either type, HbPP and HbHbPP, respectively.