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Related Experiment Video

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Testing the Efficacy of Pharmacological Agents in a Pericardial Target Delivery Model in the Swine
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Improved heart function from older donors using pharmacologic conditioning strategies.

Gayathri Kumarasinghe1, Ling Gao2, Mark Hicks3

  • 1Cardiac Transplantation Laboratory, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
|February 23, 2016
PubMed
Summary

Supplementing Celsior solution with glyceryl trinitrate, erythropoietin, and zoniporide protects older donor hearts from ischemia-reperfusion injury, improving graft function for transplantation.

Keywords:
agingextended criteria heartsischemia-reperfusion injury (IRI)myocardial preservationpharmacologic conditioning

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Area of Science:

  • Cardiology
  • Transplantation Medicine
  • Organ Preservation

Background:

  • Increasing use of older donor hearts for transplantation.
  • Older donor hearts exhibit heightened susceptibility to ischemia-reperfusion injury (IRI).
  • Higher rates of primary graft dysfunction are observed with older donor hearts.

Purpose of the Study:

  • To evaluate a pharmacologic conditioning strategy for older donor hearts.
  • To assess the protective effects of supplemented Celsior solution against IRI.
  • To improve donor heart preservation and graft function.

Main Methods:

  • Utilized Wistar rats aged 3, 12, and 18 months to model donor age.
  • Hearts were subjected to brain death and stored in Celsior or supplemented Celsior (GTN+EPO+ZON).
  • Assessed cardiac function, lactate dehydrogenase, Western blots, and histopathology post-storage.

Main Results:

  • 18-month-old hearts showed impaired function post-storage compared to 3-month-old hearts.
  • Supplemented Celsior significantly improved functional recovery in 18-month-old hearts.
  • Reduced IRI markers (lactate dehydrogenase, edema) and activated survival pathways (p-ERK1/2, p-Akt) were observed.

Conclusions:

  • Older donor hearts are vulnerable to IRI from brain death and storage.
  • Supplemented Celsior enhances cell survival signaling in older hearts.
  • This strategy effectively reduces IRI and improves donor heart preservation.