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Myocardial ischaemia reperfusion injury – applying the acid test

Victor Chang Cardiac Research Institute

Grant:
  • Cardiovascular Senior Researcher Grant
Organ System:
  • Cardiovascular
Date Funded:
  • 22 May, 2020
Chief Investigator/s:
  • Professor Peter Macdonald

Project summary

Testing the effectiveness of combining Hi1a and empagliflozin in experimental models of heart attack and of heart transplantation.

What is the issue for NSW?

Heart attack and heart failure claim the lives of 30 Australians daily. For patients suffering a heart attack, emergency transfer to hospital and urgent opening of the blocked coronary artery is the most effective treatment. However, delays in the recognition of the problem and in transferring patients to hospital—the latter compounded in rural and remote areas—reduce the amount of heart muscle that can be salvaged. For a person suffering a heart attack, “time is muscle” and every minute counts.

Heart transplantation (HTx) is the most effective treatment for advanced heart failure but is limited by donor availability. Deceased organ donation can proceed by one of two pathways – donation after brain death (DBD) or donation after circulatory death (DCD). While each pathway provides unique stresses on the donor heart, both pathways deprive the donor heart of its normal blood supply – during withdrawal of life support in the case of DCD and during transport of the heart in the case of DBD.

What does the research aim to do and how?

Recently, a peptide extracted from a funnel web spider venom was found by Professor Macdonald’s colleague, Professor Glenn King, to dramatically reduce the size of a stroke in an experimental mouse model, even when administered up to eight hours after the onset of the stroke!

There is now preliminary evidence for a similarly dramatic protective effect of this peptide, called Hi1a, in the heart in an experimental model of donor heart preservation. The team has also found that a new diabetes drug, empagliflozin, also provides potent protection of the heart in the same model. The team believes that Hi1a and empagliflozin exert their protective effect on the heart by blocking different cellular channels in the heart and that administering them in combination will provide additional protection to the heart.

In this project, the team will test the effectiveness of combining Hi1a and empagliflozin in experimental models of heart attack and of HTx. It’s believed that timely administration of these drugs may reduce the size of a heart attack by as much as 50%, even when given hours after the onset of the attack. This will result in fewer deaths caused by heart attack and fewer survivors developing heart failure. Improved preservation of the donor heart for transplantation by Hi1a and empagliflozin will result in an increase in the number and quality of donor hearts that are suitable for HTx.