# Immunosuppression after cardiac arrest and resuscitation

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $414,468

## Abstract

Abstract
Due to considerable advances in resuscitation, the number of cardiac arrest (CA) patients who survive the initial
arrest and are admitted to the intensive care unit (ICU) has been steadily increasing. However, among this growing
patient population, the morbidity and mortality rates remain unacceptably high. This has been attributed primarily to
post-CA syndrome of which an imbalanced immune response is a key component. Using our clinically relevant
murine model of CA and cardiopulmonary resuscitation (CA/CPR), we recently discovered that following
CA/CPR, there is a clear shift from the well-established acute post-CA pro-inflammatory immune response to
the less-known anti-inflammatory immune response, which eventually evolves into a severe immunosuppressive
state. Further, our preliminary data clearly support a link between this immunosuppressive state, and post-CA
infection and poor functional recovery. Importantly, this notion is corroborated by clinical observations that
infectious complications occur in a high percentage of CA survivors, and post-resuscitation infection is believed
to increase morbidity and mortality. Therefore, it is of tremendous clinical significance to better understand post-
CA immunosuppression. Our long-term goal is to develop novel therapeutic strategies to improve CA prognosis.
The objective here is to dissect mechanisms that underpin post-CA immunosuppression, and to determine the
effects of targeting post-CA immunosuppression on CA outcome, including incidence of infections and long-term
functional recovery. Notably, our pilot studies have provided compelling evidence indicating that activation of the
hypothalamic-pituitary-adrenal (HPA) axis is a primary mechanism that drives post-CA immunosuppression. Our
central hypothesis is that CA and resuscitation activates inflammasomes in the brain, which in turn activates the
HPA axis, leading to immunosuppression and poor CA outcome. This hypothesis is based on our strong
preliminary data and on substantial literature related to disease-induced immunosuppression. We will test our
central hypothesis by pursuing the following specific aims: 1) Determine the role of the HPA axis in post-CA
immunosuppression; 2) Determine the role of inflammasomes in post-CA immunosuppression via the HPA axis;
and 3) Determine the effects of modulating post-CA immunosuppression on CA outcomes. The proposed
research is significant because knowledge we will gain from this study is expected to inform future development
of new post-resuscitation care strategies to mitigate detrimental effects of post-CA immune dysfunction and thus,
improve overall CA prognosis.

## Key facts

- **NIH application ID:** 10367177
- **Project number:** 1R01HL157354-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Wei Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $414,468
- **Award type:** 1
- **Project period:** 2022-01-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10367177

## Citation

> US National Institutes of Health, RePORTER application 10367177, Immunosuppression after cardiac arrest and resuscitation (1R01HL157354-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10367177. Licensed CC0.

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