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Updated: Aug 16, 2026
In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model
Published on: October 27, 2020
Myocardial function following cold ischemic storage is improved by cardiac-specific overexpression of A1-adenosine
Marguerite Crawford1, Sara Ford, Michele Henry
1Department of Pediatrics, Division of Cardiology, Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia 22908, USA.
Insights
Overexpressing adenosine receptors (A1AR) in hearts improves their tolerance to extended cold storage for transplantation. This enhanced preservation may increase the availability of donor hearts for patients needing transplants.
Area of Science:
- Cardiology
- Transplantation Medicine
- Molecular Biology
Background:
- Current heart preservation for transplantation is limited to 4-6 hours.
- Extending cold ischemic storage time could expand the donor heart pool.
- Adenosine receptors, specifically A1AR, show potential for protecting hearts against ischemic injury.
Purpose of the Study:
- To investigate if A1AR overexpression enhances heart tolerance to prolonged cold ischemic preservation.
- To test the hypothesis that increased A1AR levels improve myocardial protection during extended ischemia.
Main Methods:
- Isolated hearts from wild type and A1AR-overexpressing transgenic mice were used.
- Hearts underwent 18 hours of cold storage (5°C in University of Wisconsin solution) followed by 2 hours of reperfusion.
- Ventricular function was assessed by measuring left ventricular pressures; cell viability by infarct size and apoptosis.
Main Results:
- A1AR-overexpressing hearts demonstrated improved function post-ischemia, with lower end-diastolic pressure and better recovery of developed pressure.
- Significant reductions in infarct size and myocardial apoptosis were observed in A1AR-overexpressing hearts.
- These findings indicate enhanced cardioprotection in hearts with A1AR overexpression.
Conclusions:
- Overexpression of cardiac A1AR provides significant cardioprotection during extended cold ischemic preservation.
- This strategy holds promise for improving heart transplant outcomes by extending organ viability.
- Targeting A1AR may be a viable approach to increase the donor heart supply.
Abstract:
Cold ischemic storage of hearts for transplantation is limited to 4-6 h, and therefore the development of strategies to extend preservation time may increase the donor pool of hearts. Overexpression of A1-adenosine receptors (A1AR) can protect hearts from acute ischemic injury, and the purpose of this study was to test the hypothesis that overexpression of A1AR will improve tolerance to longer periods of cold ischemic preservation. Hearts from 18 wild type and 16 transgenic mice with overexpression of A1AR (A1AR Trans) were isolated and perfused, and then subjected to 18 h of preservation in 5 degrees C University of Wisconsin solution followed by 2 h of reperfusion. Left ventricular end diastolic pressure and left ventricular developed pressure were measured as indices of ventricular function. Cell viability was assessed by determination of infarct size and myocardial cell apoptosis. A1AR Trans hearts showed improved function following 18 h of ischemia, as shown by lower end diastolic pressure (p < 0.05) and higher recovery of left ventricular developed pressure (p < 0.05) during reperfusion. A1AR Trans hearts had markedly reduced infarct size (p < 0.05) and decreased apoptosis (p < 0.05). Overexpression of cardiac A1AR imparts cardioprotection during long-term cold ischemic preservation.
