Insensitivity of cerebral oxygen transport to oxygen affinity of hemoglobin-based oxygen carriers

Abstract

The cerebrovascular effects of exchange transfusion of various cell-free hemoglobins that possess different oxygen affinities are reviewed. Reducing hematocrit by transfusion of a non-oxygencarrying solution dilates pial arterioles on the brain surface and increases cerebral blood flow to maintain a constant bulk oxygen transport to the brain. In contrast, transfusion of hemoglobins with P 50 of 4-34 Torr causes constriction of pial arterioles that offsets the decrease in blood viscosity to maintain cerebral blood flow and oxygen transport. The autoregulatory constriction is dependent on synthesis of 20-HETE from arachidonic acid. This oxygen-dependent reaction is apparently enhanced by facilitated oxygen diffusion from the red cell to the endothelium arising from increased plasma oxygen solubility in the presence of low or high-affinity hemoglobin. Exchange transfusion of recombinant hemoglobin polymers with P 50 of 3 and 18 Torr reduces infarct volume from experimental stroke. Cell-free hemoglobins do not require a P 50 as high as red blood cell hemoglobin to facilitate oxygen delivery.

Impact of Hemoglobin Concentration and Affinity for Oxygen on Tissue Oxygenation: The Case of Hemoglobin‐Based Oxygen Carriers

“…Current investigations also address the hypothesis that Hb is a NO transporter (7) that responds to changes in the Hb oxygenation state (8) and helps NO export out of the RBC promoting local vasorelaxation and improving VO 2 upon Hb deoxygenation (9). Constant RBC capillary transit time with negligible blood flow autoregulation. However, recent work addressed cerebral blood flow autoregulation as a sensitive mechanism to tune the blood O 2 transport in response to the body/organ needs (10,11). The described model cannot assess where exactly O 2 unloading in the capillary bed occurs, e.g., in the precapillary area or elsewhere, while it is well appreciated that O 2 unloaded in the precapillary contributes to vasoconstriction rather than tissue oxygenation (12).…”

“…Constant RBC capillary transit time with negligible blood flow autoregulation. However, recent work addressed cerebral blood flow autoregulation as a sensitive mechanism to tune the blood O 2 transport in response to the body/organ needs (10,11).…”

A bovine hemoglobin-based oxygen carrier as pump prime for cardiopulmonary bypass: Reduced systemic lactic acidosis and improved cerebral oxygen metabolism during low flow in a porcine model

“…Hemoglobin in solution increases the oxygen-carrying capacity of the plasma phase, decreases the oxygen diffusion resistance, and facilitates oxygen delivery to tissue beds. 1,2 HBOC-201 is a high P 50 (pressure of oxygen that causes the hemoglobin to be 50% saturated) HBOC: the P 50 of HBOC-201 is 38 mm Hg compared with 27 mm Hg for human intraerythrocytic hemoglobin (Table 1). This decreased affinity enhances oxygen offloading to tissues.…”