# Consequences of Cardiac Arrest: Brain Injury

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $550,448

## Abstract

Cardiac arrest (CA) has devastating consequences, even with successful resuscitation survival rates are low
and unfavorable outcomes in survivors are rampant which are almost uniformly secondary to brain injury. Our
long-term research program studies the effects of global brain ischemia resulting from CA. In the first research
phase, we developed and extensively validated measures of brain injury after CA. In the second phase, we
embarked on demonstrating therapeutic solutions for major neurologic deficit. While high quality of
cardiopulmonary resuscitation (CPR) has been shown to improve systemic perfusion, specific and validated
guidelines related to post-CA brain perfusion and blood pressure management are non-existent (1-3). Our key
hypothesis, laying the foundation for this proposal, is that brain function and neurologic outcome are dependent
on the state of cerebrovascular autoregulation (CVAR). CVAR maintains a homeostatic cerebral blood flow
(CBF) within a mean arterial pressure (MAP) range and protects the brain from injury during extremes of pressure
and flow. After global hypoxic ischemic injury, CVAR is often impaired or absent. There is a need to develop
direct measures of CVAR and validate it rigorously. Our central hypothesis is that individualizing MAP, CBF
and hypothermia management as guided by CVAR monitoring will minimize brain injury and improve
neurologic outcome. We have 5 aims. Aim 1: we will develop a miniature multicontrast microscope to
continuously interrogate CVAR and COx throughout the post-CA recovery period. We acquired EEG measures,
acute and late neuropathologic studies, early and long-term behavioral analyses as well as blood-based vascular
biomarkers to objectively calibrate our CVAR (and COx) measures with neurologic outcomes. Aim 2, we will
determine the relationship between CVAR dysfunction and post-CA whole brain injury as assessed by novel MRI
based hemodynamic, oxygenation and metabolic biomarkers. Therefore, our aims 1 and 2 will enable us to
characterize CVAR as a real time therapeutic guide as well as a prognosticator of outcome. For aims 3, 4 and
5, we will apply therapeutic maneuvers to restore and optimize CVAR as measured by the technologies
developed in aims 1 and 2. Aim 3: we will focus on post-CPR MAP management and titrate MAP for optimal
CVAR with epinephrine and nitroglycerine infusion to increase and decrease MAP respectively to improve
neurologic outcomes. Aim 4: we study the effect CBF augmentation using low power therapeutic ultrasound.
Aim5: We will focus on post-CA targeted temperature management therapy (TTM) and study the effects of
titrating temperature on normalizing CVAR slope/shift. In summary, our proposal develops new technologies and
therapies to address a critical knowledge gap in post-CPR CVAR management. We hope that our fundamental
work will potentially translate into modified clinical practices for CA management in which, beyond rescuing the
heart function, makes the brain...

## Key facts

- **NIH application ID:** 9980972
- **Project number:** 5R01HL071568-16
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Romergryko Geocadin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $550,448
- **Award type:** 5
- **Project period:** 2003-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980972

## Citation

> US National Institutes of Health, RePORTER application 9980972, Consequences of Cardiac Arrest: Brain Injury (5R01HL071568-16). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980972. Licensed CC0.

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