The Relationship of Oxygen Transport and Cardiac Index for the Prevention of Sickle Cell Crises

The formation of deoxyhemoglobin S (deoxy Hb S) polymers is the key triggering event for the complex pathophysiologic manifestations of sickle cell anemia (SCA) This polymer formation is associated with a marked right shifted oxyhemoglobin dissociation curve (decreased affinity increased P-50) which results in a decrease in arterial oxygen saturation (SaO(2)) There is a delay period ("delay time") from the formation of deoxy Hb S to polymerization that is markedly sensitive (to the power of 30 40) to the concentration and solubility changes of deoxy Hb S Deoxy Hb S polymer formation leads to sickle cell vaso occlusion a unique characteristic of SCA This theoretical study which views SCA as a disease of oxygen transport provides a novel framework to suggest that a small to modest increase in cardiac index (by decreasing the P-50 and thus increasing the SaO(2)) could change the distribution of the delay times (sec) such that the balance between occlusion and opening of microcirculatory vessels is shifted favoring the opening of these vessels therefore disfavoring vaso occlusion Our approach integrates a mathematical model of oxygen transport in SCA with (1) the expression relating the solubility of deoxy Hb S to SaO(2) and (2) the kinetic expression relating the delay time to the solubility of deoxy-Hb S