Effect of an Allosteric Modifier of Hemoglobin, RSR-4, on Oxygen Affinity and Oxygen Saturation of Hemoglobin in Rabbits

Abstract

Theoretically, if the arterial partial oxygen pressure (PaO₂) does not change, a right shift in the oxygen equilibrium curve (OEC) of hemoglobin should reduce arterial oxygen saturation. In this study we investigate whether a right shift in the OEC of hemoglobin decreases transcutaneous oxygen saturation (Tc-SO₂) following the administration of an allosteric effector, 2-[4-(((3, 5-dichloroanilino)-carbonyl) methyl) phenoxy]-2-methylpropionic acid (RSR-4). The effect of RSR-4 on hemoglobin oxygen affinity was studied in four New Zealand white male rabbits. Following intraperitoneal administration of RSR-4, Tc-SO₂ decreased in a dose-dependent manner. P₅₀ (partial oxygen pressure at 50% hemoglobin oxygen saturation) in whole blood increased as the concentration of RSR-4 increased. Tc-SO₂ decreased as whole-blood affinity (1/P₅₀) decreased. There was no positive correlation between Tc-SO₂ and PaO₂. We concluded that a decrease in hemoglobin oxygen affinity following RSR-4 administration reduced arterial oxygen saturation. This decrease in the presence of an allosteric effector such as RSR-4 in vivo can be detected and monitored as a reduction in Tc-SO₂.