# Protection of transplanted heart function by regulation of Na/K pump activity

> **NIH NIH R41** · WR BIOTECH, LLC · 2023 · $275,739

## Abstract

The objective of this proposal is to examine a novel technique called improved Synchronization Modulation
Electric Field (i-SMEF) in the protection of donor hearts and improvement of transplanted graft functions. We will
apply the i-SMEF on donor hearts during static cold storage and evaluate the transplanted graft function following
heart transplantation in mice.
 Heart transplantation (HTx) remains the best therapeutic option for advanced-stage heart failure, as well as
for complex congenital heart disease, restrictive cardiomyopathy, and some infectious diseases. However, the
long-term survival rate of the heart graft has only shown a small improvement during the past decades, with a
median survival about 12.5 years. In addition, the maximal time for static cold storage is usually about 5 hours.
Longer storage time is associated with higher rates of both early and late graft failure. The development of new
strategy for extension of storage time thereby increasing the donor pool and improvement of the transplanted
graft function are unmet needs.
 One of the prominent challenges in HTx is ischemia reperfusion injury (IRI) to the graft. IRI is a major factor
for both early and late graft failure and mortality. Following hypoxia, due to poor ATP supply, activity of the
Na+/K+-ATPase (Na/K pump) slows down or stops, which is one of the earliest and critical impairments following
ischemia. Reduction in the Na/K pump function disrupts the equilibrium of cellular ion concentrations, cell volume
and membrane potential, which can cause damage to all cellular components (e.g., mitochondria), apoptosis
and necrosis. Therefore, maintaining the Na/K pump function following ischemia could be a vital initial strategy
for the protection or prevention of the ischemic injury.
 We have developed a novel technique, named the i-SMEF (patent pending, Chen and Liu), which can not
only maintain the pump functions, but also generate ATP molecules.
 Based on strong preliminary findings, we propose to test this technique in a mouse HTx model. We will test
our hypothesis that application of the i-SMEF on donor hearts during cold storage protects against ischemic
injury and improves the transplanted graft functions.

## Key facts

- **NIH application ID:** 10691960
- **Project number:** 1R41HL165958-01A1
- **Recipient organization:** WR BIOTECH, LLC
- **Principal Investigator:** WEI CHEN
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $275,739
- **Award type:** 1
- **Project period:** 2023-09-07 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10691960

## Citation

> US National Institutes of Health, RePORTER application 10691960, Protection of transplanted heart function by regulation of Na/K pump activity (1R41HL165958-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10691960. Licensed CC0.

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