ENGINEERED ERYTHROCYTES - INFLUENCE OF P-50 RIGHTWARD SHIFT AND OXEMIA ON OXYGEN-TRANSPORT TO TISSUES

The red blood cell (RBC) membrane may be reversibly opened using a lys is-resealing continuous flow method. The technology was adapted to the internalisation of an allosteric effector of haemoglobin, Inositol-He xaphosphate (IHP). This molecule, occupying the allosteric site of 2,3 Bis-Phosphoglycerate with a very large affinity, induces a rightward shift of the oxyhaemoglobin dissociation curve (ODC). From ODC paramet ers in human volunteers, the potential effect of P-50 (oxygen pressure at 50% haemoglobin saturation) on oxygen exchangeable fraction (OEF%) , for various oxygen partial pressures (oxemia) was evaluated. For hyp eroxic or normoxic arterial oxygen pressure (paO(2)), rightward shift greatly improved OEF%. In optimised conditions, engineered erythrocyte s were potentially able to deliver two to three times more oxygen than normal cells. For patients with decreased paO(2), as observed in chro nic obstructive pulmonary deficiency (COPD), the reduction in arterial oxygen saturation (saO(2)%) reduces the benefit of the treatment for paO(2) values between 60 and 80 mmHg. Below 60 mmHg, the saO(2)% reduc tion cannot be compensated by a corresponding reduction in svO(2)%, pa rticularly for organs with physiologically low svO(2)%. In these organ s, deleterious effects could be observed for a very large rightward sh ift of the ODC. Such engineered cells have unique properties for oxyge n transport improvement and may be used for the treatment of patients suffering from diseases associated with hypoxia and ischemia.