# New Approaches to Mitigate Left Ventricular Injury with VA-ECMO in Acute Myocardial Infarction

> **NIH NIH R01** · TUFTS MEDICAL CENTER · 2022 · $845,104

## Abstract

This new RO1 proposal explores novel mechanisms of cardioprotection involving veno-arterial membrane
oxygenation (VA-ECMO) as a platform to reduce myocardial damage after acute myocardial infarction (AMI).
Use of VA-ECMO has grown exponentially in AMI over the past decade, however the impact of VA-ECMO on
myocardial injury has not been rigorously studied. New mechanistic insight into the effect of VA-ECMO on
reperfusion injury is needed. We recently reported the critical observation that VA-ECMO increases infarct size
in swine models of AMI and in new data have now identified a novel paradigm whereby VA-ECMO depletes
critical regulators of mitochondrial function and worsens heart damage in AMI. By employing highly translational
large animal models and clinically relevant interventional approaches, we will now explore new mechanisms
involving VA-ECMO and myocardial reperfusion injury, provide penetrating insight into cardioprotection, and
generate proof of concept data for the development of new therapeutic approaches to limit left ventricular (LV)
injury in AMI. The PI is an interventional cardiologist and advanced heart failure specialist who studies molecular
mechanisms of cardiac remodeling, reperfusion injury, and the hemodynamic effects of circulatory support
pumps. The current proposal integrates expertise in coronary and ventricular physiology, mechanical circulatory
support, molecular biology, and interventional cardiology to the field of myocardial reperfusion injury, for which
no specific therapy currently exists. We will test the novel hypothesis that VA-ECMO promotes myocardial
damage by worsening myocardial oxygen supply-demand mismatch through increased LV wall stress and
hyperoxemia-mediated injury resulting in loss of mitochondrial integrity and further that targeting these
mechanisms will reduce infarct size in AMI. Exciting new preliminary data show that LV decompression or
targeting normal arterial oxygen tension during VA-ECMO support can mitigate LV injury by reducing myocardial
oxygen demand and increasing coronary blood flow. We observed for the first time that VA-ECMO decreases
levels of tafazzin, a key enzyme controlling maturation of cardiolipin (CL), a master regulator of mitochondrial
integrity. In exciting new findings, treatment with elamipretide, a CL-stabilizing compound, before initiation of VA-
ECMO significantly reduced infarct size compared to reperfusion alone. These pioneering approaches address
major knowledge gaps by studying the effect of VA-ECMO on ventricular load, coronary blood flow and overcome
critical barriers associated with cardioprotection in AMI. To test our hypothesis we will employ translational
studies in swine models to determine the impact of VA-ECMO on myocardial blood flow (SA1), mitochondrial
integrity (SA2), and to test the therapeutic utility of a combined drug-device approach (SA3) to limit adverse
cardiac remodeling after AMI. This proposal has tremendous potential to impact our unde...

## Key facts

- **NIH application ID:** 10454891
- **Project number:** 5R01HL159089-02
- **Recipient organization:** TUFTS MEDICAL CENTER
- **Principal Investigator:** Navin Kumar Kapur
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $845,104
- **Award type:** 5
- **Project period:** 2021-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454891

## Citation

> US National Institutes of Health, RePORTER application 10454891, New Approaches to Mitigate Left Ventricular Injury with VA-ECMO in Acute Myocardial Infarction (5R01HL159089-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10454891. Licensed CC0.

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