# Restoration and Function of S-Nitrosothiol in Stored Blood

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $549,410

## Abstract

PROJECT SUMMARY
The therapeutic benefit of transfusion presumes a direct correlation between blood oxygen carrying capacity
and oxygen delivery. However, studies have shown that stored blood loses its ability to oxygenate tissues. The
sequelae that can occur after transfusion (renal injury, myocardial infarction, death) are consistent with the idea
that banked blood may exacerbate rather than correct anemia-induced hypoxia.
We have discovered that banked blood has markedly diminished levels of nitric oxide/S-nitrosothiol (NO/SNO)
bioactivity including reduced amounts of the S-nitrosylated form of hemoglobin (SNO-Hb), a major mediator of
blood flow and peripheral oxygen delivery. This decline in SNO provides a mechanistic basis for the impaired
vasodilatory activity of stored red blood cells (RBCs) and an explanation for why transfusion of even small
amounts of blood may impair tissue perfusion. We have built on this novel finding by demonstrating that
restoration of SNO-Hb levels (renitrosylation) corrects storage-induced deficiencies in RBC oxygen delivery
and transfusion-induced organ dysfunction in multiple preclinical transfusion paradigms, and we have initiated
clinical studies to assess the effects of transfusion on human tissue oxygenation. We have also developed
first-in-class renitrosylating agents that are already undergoing clinical testing.
We are positioned to provide critically needed data on the effects of transfusion on tissue oxygenation in
humans and to advance the benefits of renitrosylation therapy on oxygen delivery through the following aims:
 1. To advance understanding of the molecular mechanisms by which RBCs deploy SNO-based signals to
 regulate tissue oxygenation in fresh and stored blood.
 2. To develop a device for ex vivo renitrosylation.
 3. To determine if the physiologic responses to transfusion with renitrosylated RBCs are superior to
 untreated banked blood in a preclinical trauma model.
 4. To conduct an autologous standard flow (i.e. non-trauma) transfusion study in humans with and without
 renitrosylation to delineate the physiologic effects of transfusion and the benefits of increased/restored
 SNO-Hb levels on tissue oxygenation.
Collectively, our studies will provide much-needed insight into the effects of transfusion on tissue oxygenation,
shed light on the mechanistic basis of adverse ischemic events associated with transfusion, and accelerate
development of therapeutic approaches (repletion of SNO-Hb). Restoration of the oxygen delivery capabilities
of banked blood should result in blood transfusion achieving its clinical purpose: vasodilation in the
microcirculation to improve end-organ oxygen delivery in the anemic patient. To the extent that the world's
supplies of banked RBCs are deficient in SNO-Hb, renitrosylation may hold significant therapeutic promise.

## Key facts

- **NIH application ID:** 9984503
- **Project number:** 5R01HL126900-05
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** JONATHAN S. STAMLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $549,410
- **Award type:** 5
- **Project period:** 2016-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984503

## Citation

> US National Institutes of Health, RePORTER application 9984503, Restoration and Function of S-Nitrosothiol in Stored Blood (5R01HL126900-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984503. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*