Pharmacologic Targeting of Red Blood Cells to Improve Tissue Oxygenation.
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2017-12-14
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Disruption of microvascular blood flow is a common cause of tissue hypoxia in disease, yet no therapies are available that directly target the microvasculature to improve tissue oxygenation. Red blood cells (RBCs) autoregulate blood flow through S-nitroso-hemoglobin (SNO-Hb)-mediated export of nitric oxide (NO) bioactivity. We therefore tested the idea that pharmacological enhancement of RBCs using the S-nitrosylating agent ethyl nitrite (ENO) may provide a novel approach to improve tissue oxygenation. Serial ENO dosing was carried out in sheep (1-400 ppm) and humans (1-100 ppm) at normoxia and at reduced fraction of inspired oxygen (FiO2 ). ENO increased RBC SNO-Hb levels, corrected hypoxia-induced deficits in tissue oxygenation, and improved measures of oxygen utilization in both species. No adverse effects or safety concerns were identified. Inasmuch as impaired oxygenation is a major cause of morbidity and mortality, ENO may have widespread therapeutic utility, providing a first-in-class agent targeting the microvasculature.
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Reynolds, James D, Trevor Jenkins, Faisal Matto, Ryan Nazemian, Obada Farhan, Nathan Morris, John M Longphre, Douglas T Hess, et al. (2017). Pharmacologic Targeting of Red Blood Cells to Improve Tissue Oxygenation. Clin Pharmacol Ther. 10.1002/cpt.979 Retrieved from https://hdl.handle.net/10161/16052.
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Richard Edward Moon
Research interests include the study of cardiorespiratory function in humans during challenging clinical settings including the perioperative period, and exposure to environmental conditions such as diving and high altitude. Studies have included gas exchange during diving, the pathophysiology of high altitude and immersion pulmonary edema, the effect of anesthesia and postoperative analgesia on pulmonary function and monitoring of tissue oxygenation. Ongoing human studies include the effect of respiratory muscle training on chemosensitivity and blood gases during stressful breathing: underwater exercise.
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