Pharmacologic Targeting of Red Blood Cells to Improve Tissue Oxygenation.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Reynolds, JD; Jenkins, T; Matto, F; Nazemian, R; Farhan, O; Morris, N; Longphre, JM; Hess, DT; Moon, RE; Piantadosi, CA; Stamler, JS

Published Date

  • September 2018

Published In

Volume / Issue

  • 104 / 3

Start / End Page

  • 553 - 563

PubMed ID

  • 29238951

Pubmed Central ID

  • 29238951

Electronic International Standard Serial Number (EISSN)

  • 1532-6535

Digital Object Identifier (DOI)

  • 10.1002/cpt.979

Language

  • eng

Conference Location

  • United States