# Feasibility of expanding ischemia time for hearts destined for transplantation

> **NIH NIH R43** · TISSUE TESTING TECHNOLOGIES, LLC · 2020 · $386,026

## Abstract

In collaboration with Prof. Brandacher at Johns Hopkins University we plan to improve the currently most used
clinical method of heart preservation, namely hypothermia at 0 to +4°C. We will build upon our base
preservation formulation, Unisol™, that has been shown to preserved whole large animals below +10°C for 6-
8h after total blood replacement with Unisol™ with normal functions upon return to physiological
conditions. We have also shown that Unisol™ can maintain blood vessel function for at least 6 days at both -7°
C and +4°C and that mouse hearts stored at +4°C for 18 hours in Unisol™ have a significantly faster return of
heart function than hearts stored in the gold standard hypothermic heart preservation solution Celsior (HTK).
Encouraged by these results we propose evaluation of Unisol supplemented with reagents targeting oxidation,
apoptosis (enhancers of stress tolerance) and metabolism (metabolic rate inhibition) in 2 specific aims using a
human cardiac myocyte cell line to select optimal reagent concentrations in vitro and a heterotopic heart
transplant model to evaluate the best supplement formulations developed in the in vitro studies. The lead in
vitro assay will be alamarBlue, however outcomes will be checked using alternative assays including trypan
blue, live/dead stain and MTT assay. Apoptosis will be evaluated if significant losses of metabolic activity are
observed 1 to 2 days after return to physiologic culture conditions. MALDI tissue imaging and proteomics will
be performed on selected control and best performing hearts to provide molecular mapping information on
metabolites, lipids, enzymatic products, and post translational modifications in heart sections. The in vivo
studies will evaluate the best formulations from the in vitro studies over 7 days of hypothermic storage using a
syngeneic BALB/C mouse, heterotopic transplantation model. Controls hearts will be preserved in high K+
Unisol™ (UHK) and HTK. We anticipate that the supplemented formulation will maintain viability and
function of hearts for at least 36 hours, a considerable improvement over all current practice methods. Based
upon preliminary data with blood vessel preservation, heart storage times of 6-7 days may be obtained. This
innovation will not only increase storage time, it will also provide the opportunity for more closely matched
recipients and potentially induction of tolerance. Furthermore, we are improving on the most tried and
true method for hypothermic heart storage in clinical practice that is relatively inexpensive and easy
to ship by air. Demonstration of ≥36 hours of hypothermic storage with retention of heart function will be
considered to be a successful demonstration of feasibility for progression to a Phase II SBIR proposal for
further evaluation in large animal models and ex vivo human heart evaluation post-preservation.

## Key facts

- **NIH application ID:** 10082625
- **Project number:** 1R43HL152941-01A1
- **Recipient organization:** TISSUE TESTING TECHNOLOGIES, LLC
- **Principal Investigator:** Kelvin G.M. Brockbank
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,026
- **Award type:** 1
- **Project period:** 2020-09-23 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10082625

## Citation

> US National Institutes of Health, RePORTER application 10082625, Feasibility of expanding ischemia time for hearts destined for transplantation (1R43HL152941-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10082625. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*