The dose-dependent effect of RSR13, a synthetic allosteric modifier of hemoglobin, on physiological parameters and brain tissue oxygenation in rats.

RSR13 is a synthetic allosteric modifier of hemoglobin that decreases the oxygen-binding affinity of hemoglobin, increasing the P50. As a result, tissue oxygen tension is expected to increase. Using the capabilities of in vivo EPR, we directly examined the effect of RSR13 on brain pO(2) in rats and the relationship between any change in brain oxygenation and changes in physiological parameters, including blood gases. The brain pO(2) and arterial blood p(a)O(2) were increased significantly (p<0.005) following RSR13 administration. The peak increase of brain tissue pO(2) was 8.8 +/- 1.2 mm Hg in the animals receiving 150 mg/kg RSR13 and 13 +/- 3 mm Hg in the animals receiving 300 mg/kg RSR13. There was no difference among groups in MBP, heart rate, p(a)CO(2), pH, or HCO3. These data indicate that in anesthetized rats, RSR13 dose-dependently increases brain pO(2) without affecting other physiologic parameters. This capability is likely to be very useful in circumstances where the pO(2) of the brain is compromised.