Pharmacologic Targeting of Red Blood Cells to Improve Tissue Oxygenation.

Reynolds, James D

Jenkins, Trevor

Matto, Faisal

Nazemian, Ryan

Farhan, Obada

Morris, Nathan

Longphre, John M

Hess, Douglas T

Moon, Richard E

Piantadosi, Claude A

Stamler, Jonathan S

United States

2018-02-01T18:24:16Z

2018-02-01T18:24:16Z

2017-12-14

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.

https://www.ncbi.nlm.nih.gov/pubmed/29238951

1532-6535

https://hdl.handle.net/10161/16052

eng

Wiley

Clin Pharmacol Ther

10.1002/cpt.979

Pharmacologic Targeting of Red Blood Cells to Improve Tissue Oxygenation.

Journal article

Moon, Richard E|0000-0003-4432-0332

https://www.ncbi.nlm.nih.gov/pubmed/29238951

Anesthesiology

Anesthesiology, General, Vascular, High Risk Transplant & Critical Care

Clinical Science Departments

Duke

Medicine

Medicine, Pulmonary, Allergy, and Critical Care Medicine

School of Medicine

Published online