# Protective adaptive immune mechanisms after cardiac arrest

> **NIH NIH R01** · MAINEHEALTH · 2024 · $644,111

## Abstract

Cardiac arrest induces a systemic inflammatory response. Several studies have demonstrated that increased
sustained inflammation is associated with poor outcomes, suggesting a possible role for anti-inflammatory and
immunomodulatory therapies. However, these studies have focused on mechanisms that promote
inflammation without considering protective mechanisms that are also mediated by the immune cells. Our
preliminary data from human patients with cardiac arrest revealed an association between the higher number
of CD73-expressing lymphocytes and favorable outcomes. CD73 is a key enzyme in the generation of
adenosine, a purine nucleoside that is characterized by potent anti-inflammatory properties. Our new
preliminary data generated using a mouse model of cardiac arrest and resuscitation suggest that CD73-
expressing lymphocytes play a role in the control of local inflammation in the heart and brain tissues. In
Specific Aim 1, we will determine the functional significance of adoptive cell therapy using protective CD73-
expressing lymphocytes after an ischemia and reperfusion injury in a mouse model of cardiac arrest and
cardiopulmonary resuscitation. In Specific Aim 2, we will test the hypothesis that CD73-expressing
lymphocytes form T cell-monocyte complexes and promote the differentiation of monocytes toward anti-
inflammatory macrophages. In Specific Aim 3, we will define molecular mechanisms involved in the formation
of anti-inflammatory lymphocyte-macrophages complexes. Our new data will determine the contribution of
cardiac arrest-induced inflammatory response in the heart and brain tissue damage and identify
CD73/adenosine/adenosine receptors axis as a potential therapeutic approach to improve outcomes after
global ischemia and reperfusion injury.

## Key facts

- **NIH application ID:** 10856321
- **Project number:** 1R01HL173118-01
- **Recipient organization:** MAINEHEALTH
- **Principal Investigator:** Sergey Ryzhov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $644,111
- **Award type:** 1
- **Project period:** 2024-04-02 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10856321

## Citation

> US National Institutes of Health, RePORTER application 10856321, Protective adaptive immune mechanisms after cardiac arrest (1R01HL173118-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10856321. Licensed CC0.

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