GBT1118, a compound that increases the oxygen affinity of hemoglobin, improves survival in murine hypoxic acute lung injury

Background: Acute respiratory distress syndrome (ARDS) is characterized by lung inflammation and pulmonary edema leading to arterial hypoxemia and death if the hypoxemia is severe. Strategies to correct hypoxemia have the potential to improve clinical outcomes in ARDS. The goal of this study was to evaluate the potential of hemoglobin modification as a novel therapy for ARDS-induced hypoxemia. Methods: The therapeutic effect of two different doses of GBT1118, a compound that increases the oxygen affinity of hemoglobin was evaluated in a murine model of acute lung injury induced by intra-tracheal LPS instillation 24 hours prior to exposure to 5% or 10% hypoxia. Results: As expected, administration of GBT1118 to mice significantly increased the oxygen affinity of hemoglobin. Compared to mice receiving vehicle control, mice treated with GBT1118 had significantly lower mortality after LPS+ 5% hypoxia (47% with vehicle vs. 22% with low dose GBT1118, 13% with high dose GBT1118, p=0.032 by log rank) and had redu...