# Restoration and Function of S-Nitrosothiol in Stored Blood

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $555,884

## Abstract

PROJECT SUMMARY
The therapeutic benefit of transfusion presumes a direct correlation between blood oxygen carrying capacity and
oxygen delivery. However, our preclinical and clinical studies show 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 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 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 further advance understanding of the molecular mechanisms by which RBCs export SNO bioactivity
 to regulate tissue oxygenation;
 2. To develop a device for controlled ex vivo renitrosylation;
 3. To determine if renitrosylation can improve post-surgical outcome in an animal model of pediatric bypass;
and
 4. To conduct an autologous transfusion study in humans to determine the benefits of renitrosylation on
 tissue oxygenation.
Collectively, our studies should 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:** 10818366
- **Project number:** 5R01HL126900-07
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** JONATHAN S. STAMLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $555,884
- **Award type:** 5
- **Project period:** 2016-12-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10818366

## Citation

> US National Institutes of Health, RePORTER application 10818366, Restoration and Function of S-Nitrosothiol in Stored Blood (5R01HL126900-07). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10818366. Licensed CC0.

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