Nitrosyl Hemoglobin Formation In-Vivo After Intravenous Administration of A Hemoglobin-Based Oxygen Carrier in Endotoxemic Rats

Abstract

Interaction of hemoglobin-based oxygen carriers (HBOCs) with nitric oxide (NO) of endothelium or macrophage origin has been implicated in the observed vasoconstriction of some HBOC infusion. Definitive evidence supporting this interaction, in-vivo, has not been reported. We report here a confirmed in-vivo formation of nitrosyl Hb (HbNO), a product of Hb and NO reaction, in endotoxemic rats following intravenous administration of a HBOC. Male Sprague-Dawley rats were rendered endotoxemic by intravenous injection of lipopolysaccharide (LPS, 10mg/Kg), and five hours later HBOC (1.2gHb/Kg) was infused. Changes in blood pressure (BP) and HbNO levels were followed. HBOC infusion immediately reversed the hypotension of endotoxemia. In addition, HBOC infusion caused plasma HbNO formation determined by electron paramagnetic resonance spectroscopy. This is direct evidence of NO reaction with infused Hb. In conclusion, HBOC interacts in-vivo with NO directly in a model with increased NO. Whether this effect is prese...