# Novel mechanisms and treatment of arrhythmia during resuscitation

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $668,976

## Abstract

Resuscitation from sudden cardiac arrest (SCA) is typically initiated in patients with ongoing ischemia and ventricular
fibrillation (VF) or tachycardia (VT) that, even if successful, is commonly followed by repeated rearrest. Despite significant
efforts to improve resuscitation from SCA, survival remains poor prompting NIH to identify resuscitation as a high priority
for emergency care research. Beat-to-beat alternans of cellular repolarization in the myocardium (repolarization
alternans) is a substrate for arrhythmias, is rampant during resuscitation, and is manifested on the ECG as T-wave
oscillations that can alternate (2:1) or as more complex oscillations. In preliminary studies, we observed in resuscitation
patients and in an in vivo translational model of resuscitation from SCA, that rearrest due to VT/VF is preceded by T-wave
oscillations that are complex; whereas, rearrest due to pulseless electrical activity (PEA) is preceded by increased T-wave
oscillations that alternate. Accordingly, we contend that when T-wave oscillations are complex, repolarization alternans
in the myocardium is spatially discordant, which is repolarization alternans occurring out-of-phase in adjacent regions and
is highly arrhythmogenic. In contrast, when T-wave oscillations alternate, repolarization alternans in the myocardium is
spatially in-phase (concordant), which poses no known immediate arrhythmia risk but is associated with mechanical
dysfunction and, thus, PEA. Finally, in the absence of any repolarization alternans, risk of rearrest due to PEA or VT/VF is
low. We hypothesize that during resuscitation rearrest due to VT/VF or PEA is strongly linked to repolarization alternans
in the myocardium that is spatially discordant or not, respectively, and that specifically targeting the underlying
mechanisms can prevent rearrest due to VT/VF and, possibly, PEA. In addition, the full spectrum of ECG T-wave oscillations
can be utilized to predict no rearrest and rearrest from VT/VF or PEA and, thus, be used in the future as a biomarker to
guide therapy and significantly improve outcomes. Our hypotheses will be tested with the following aims. 1) Determine
the mechanistic relationship between cellular repolarization alternans and rearrest due to VT/VF or PEA in an in vivo model
of resuscitation. 2) Determine if targeting the mechanisms of repolarization alternans can prevent rearrest during
resuscitation, thereby gaining additional mechanistic insight. 3) Develop and test an ECG biomarker for predicting risk of
rearrest due to VT/VF and PEA in resuscitation patients. To achieve these aims, we will utilize sophisticated
instrumentation and signal processing in an in vivo translational model of resuscitation as well as in pre-hospital and in-
hospital resuscitation patients. We have also established a highly translational collaboration that combines expertise in
emergency medicine, cardiac arrhythmia, and clinical electrophysiology. Our scientific environment provides...

## Key facts

- **NIH application ID:** 9886863
- **Project number:** 1R01HL142754-01A1
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** KENNETH LAURITA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $668,976
- **Award type:** 1
- **Project period:** 2020-04-10 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9886863

## Citation

> US National Institutes of Health, RePORTER application 9886863, Novel mechanisms and treatment of arrhythmia during resuscitation (1R01HL142754-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9886863. Licensed CC0.

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