Skip to main content
Journal cover image

Pharmacologic Targeting of Red Blood Cells to Improve Tissue Oxygenation.

Publication ,  Journal Article
Reynolds, JD; Jenkins, T; Matto, F; Nazemian, R; Farhan, O; Morris, N; Longphre, JM; Hess, DT; Moon, RE; Piantadosi, CA; Stamler, JS
Published in: Clin Pharmacol Ther
September 2018

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

September 2018

Volume

104

Issue

3

Start / End Page

553 / 563

Location

United States

Related Subject Headings

  • Young Adult
  • Vasodilator Agents
  • Vasodilation
  • Time Factors
  • Sheep, Domestic
  • Pharmacology & Pharmacy
  • Oxygen
  • Nitrites
  • Nitric Oxide
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Reynolds, J. D., Jenkins, T., Matto, F., Nazemian, R., Farhan, O., Morris, N., … Stamler, J. S. (2018). Pharmacologic Targeting of Red Blood Cells to Improve Tissue Oxygenation. Clin Pharmacol Ther, 104(3), 553–563. https://doi.org/10.1002/cpt.979
Reynolds, James D., Trevor Jenkins, Faisal Matto, Ryan Nazemian, Obada Farhan, Nathan Morris, John M. Longphre, et al. “Pharmacologic Targeting of Red Blood Cells to Improve Tissue Oxygenation.Clin Pharmacol Ther 104, no. 3 (September 2018): 553–63. https://doi.org/10.1002/cpt.979.
Reynolds JD, Jenkins T, Matto F, Nazemian R, Farhan O, Morris N, et al. Pharmacologic Targeting of Red Blood Cells to Improve Tissue Oxygenation. Clin Pharmacol Ther. 2018 Sep;104(3):553–63.
Reynolds, James D., et al. “Pharmacologic Targeting of Red Blood Cells to Improve Tissue Oxygenation.Clin Pharmacol Ther, vol. 104, no. 3, Sept. 2018, pp. 553–63. Pubmed, doi:10.1002/cpt.979.
Reynolds JD, Jenkins T, Matto F, Nazemian R, Farhan O, Morris N, Longphre JM, Hess DT, Moon RE, Piantadosi CA, Stamler JS. Pharmacologic Targeting of Red Blood Cells to Improve Tissue Oxygenation. Clin Pharmacol Ther. 2018 Sep;104(3):553–563.
Journal cover image

Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

September 2018

Volume

104

Issue

3

Start / End Page

553 / 563

Location

United States

Related Subject Headings

  • Young Adult
  • Vasodilator Agents
  • Vasodilation
  • Time Factors
  • Sheep, Domestic
  • Pharmacology & Pharmacy
  • Oxygen
  • Nitrites
  • Nitric Oxide
  • Male