# Pharmacological Induced Torpor/Hypothermia As A Novel Therapy for Improving Post Cardiac Arrest Resuscitation Outcomes

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2020 · $395,000

## Abstract

ABSTRACT
Cellular injury from oxygen and nutrient deprivation (ischemic injury) occurs following heart attacks and strokes
and is a major cause of death and disability. Cooling (hypothermia) patients to slow metabolism and limit
cellular injury from ischemic injury is done to protect the heart and brain in cardiac surgery and following
cardiac arrest. Inducing hypothermia is physically difficult and time consuming particularly in emergent
situations, creating a barrier to its broader use. In addition, there is a large need to optimize the timing and
depth of hypothermia for cellular protection while investigating the mechanisms of how hypothermia protects
cells from injury. This project attempts to overcome these barriers by testing a novel chemical found in the
blood stream of hibernating animals that induces torpor (hypo-metabolism/hypothermia) within minutes.
Specifically, this project tests the hypothesis that pharmacological induction of torpor/hypothermia with
5’adenosine monophosphate (AMP) will improve post-CA outcomes by simultaneously activating AMP
activated kinase (AMPK), while inhibiting the mitochondrial fission protein Dynamin related protein 1 (Drp1),
thereby reversing myocardial stunning through improved mitochondrial and metabolic function. My preliminary
data demonstrate that this chemical, 5’AMP rapidly induces hypothermia and cardioprotection within minutes of
administration. Aim 1 tests the effects of 5’AMP on improving cardiac arrest outcomes in multiple models of
ischemia/reperfusion injury, while optimizing the conditions of hypothermia. Aim 2 tests whether the effects of
5’AMP are mediated by AMPK through the use of mice with genetically attenuated or overexpressing AMPK.
Finally, Aim 3 determines whether Drp1 expression is necessary for post-cardiac arrest mitochondrial and
myocardial dysfunction. Success of this research will establish a new method for rapidly inducing hypothermia
while identifying AMPK and Drp1 as new therapeutic targets for post cardiac arrest and ischemic injury.

## Key facts

- **NIH application ID:** 9918959
- **Project number:** 5R01HL133675-05
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Willard William Sharp
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $395,000
- **Award type:** 5
- **Project period:** 2016-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9918959

## Citation

> US National Institutes of Health, RePORTER application 9918959, Pharmacological Induced Torpor/Hypothermia As A Novel Therapy for Improving Post Cardiac Arrest Resuscitation Outcomes (5R01HL133675-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9918959. Licensed CC0.

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