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 pO2 in rats and the relationship between any change in brain oxygenation and changes in physiological parameters, including blood gases. The brain pO2 and arterial blood paO2 were increased significantly (p < 0.005) following RSR13 administration. The peak increase of brain tissue pO2 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, paCO2, pH, or HCO3. These data indicate that in anesthetized rats, RSR13 dose-dependently increases brain pO2 without affecting other physiologic parameters. This capability is likely to be very useful in circumstances where the pO2 of the brain is compromised.
Grinberg
Oleg Y
OY
EPR Center for the Study of Viable Systems, Dept. of Radiology, Dartmouth Medical School, 7785 Vail, Hanover, NH 03755, USA.
Miyake
Minoru
M
Hou
Huagang
H
Steffen
Robert P
RP
Swartz
Harold M
HM
D000494:Allosteric Regulation; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D006339:Heart Rate; D006454:Hemoglobins / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000814:Aniline Compounds; D006454:Hemoglobins; D011422:Propionates; C067396:efaproxiral; D010100:Oxygen