# ECPR After Prolonged Cardiac Arrest:  Targeting Mechanisms of the No-Reflow

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $751,384

## Abstract

Project Summary/Abstract
Over 400,000 patients are treated for sudden cardiac arrest each year in the U.S., but fewer than 1 in 5 survive
after in-hospital cardiac arrest (IHCA), and fewer than 1 in 10 survive after out-of-hospital cardiac arrest (OHCA).
The overwhelming majority of deaths are caused by failure to achieve return of spontaneous circulation (ROSC)
using standard cardiopulmonary resuscitation (CPR) and advanced cardiovascular life support (ACLS).
Extracorporeal cardiopulmonary resuscitation (ECPR) using percutaneous veno-arterial extracorporeal
membrane oxygenation (ECMO) is rapidly emerging as a feasible and effective resuscitation strategy for patients
that fail standard resuscitation efforts. It is estimated that up to 10% of treated OHCA and IHCA patients are
potential candidates for ECPR, and widespread implementation could save up to 10,000 lives each year in the U.S.
Although return of a spontaneous heartbeat can be initially achieved in most patients with ECPR, less than one
third survive with good neurologic outcomes. Therefore, more research is needed to maximize the potential of
this life saving therapy. A fundamental barrier to the success of ECPR after prolonged cardiac arrest is the “no-
reflow phenomenon,” defined as inadequate vital organ reperfusion despite restoring normal cardiac output. This
project's central hypothesis is that intravascular complications of total-body ischemia and reperfusion, including
microvascular coagulation, leukocyte-adhesion, and neutrophil extracellular trap (NET) formation cause no-
reflow and prevent recovery of heart and brain function when ECPR is used to treat prolonged cardiac arrest.
Our proposed Specific Aims will test this hypothesis in a clinically relevant swine model of ECPR after prolonged
cardiac arrest that is established in the UM investigator laboratories. Aim 1 will elucidate the impact of
intravascular coagulation on recovery of heart and brain function after prolonged cardiac arrest treated with
ECPR. Experiments will: 1) compare the effectiveness of indirect (heparin) and direct (argatroban) thrombin
inhibition early during CPR and 2) evaluate the effectiveness of thrombolytic therapy (streptokinase) at initiation
of ECPR. Aim 2 will examine the impact of leukocyte-mediated inflammation on recovery of heart and brain
function after prolonged cardiac arrest treated with ECPR. Proposed experiments will compare the effectiveness
of standard leukocyte filtration to our novel leukocyte modulation (L-MOD) device during ECPR. Aim 3 will
determine the impact of therapies identified in Aim 1 and Aim 2 on 7-day survival, cardiovascular function, and
neurologic function after prolonged cardiac arrest treated with ECPR. Overall, the results of these aims will
advance the field by providing new fundamental knowledge about the mechanisms of no-reflow and proof-of-
concept evidence that therapeutic strategies effectively targeting “no-reflow” improve outcomes with ECPR after
prolon...

## Key facts

- **NIH application ID:** 9956612
- **Project number:** 5R01HL133129-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Robert H. Bartlett
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $751,384
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9956612

## Citation

> US National Institutes of Health, RePORTER application 9956612, ECPR After Prolonged Cardiac Arrest:  Targeting Mechanisms of the No-Reflow (5R01HL133129-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9956612. Licensed CC0.

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