Ischemia and reperfusion injury to mitochondria and cardiac function in donation after circulatory death hearts- an experimental study
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Published on: November 3, 2023
Oluwatoyin Akande1, Qun Chen2, Stefano Toldo2
1Department of Surgery, Virginia Commonwealth University, Richmond, VA, United States of America.
Insights
Donation after circulatory death (DCD) hearts show impaired mitochondrial function and reduced cardiac performance due to ischemia and reperfusion injury. Interventions targeting mitochondria could make DCD hearts viable for transplantation.
Area of Science:
- Cardiology
- Transplantation Medicine
- Mitochondrial Biology
Background:
- Heart transplantation is the definitive treatment for end-stage heart failure.
- Limited donor heart availability restricts transplantation, necessitating expanded donor pools.
- Donation after circulatory death (DCD) offers a potential solution but faces challenges from ischemia-reperfusion injury.
Purpose of the Study:
- To investigate the impact of ischemia and reperfusion on mitochondria and cardiac function in DCD rat hearts.
- To compare DCD hearts with control beating-heart donor (CBD) hearts.
Main Methods:
- Rat hearts were procured using either CBD or DCD protocols.
- DCD hearts underwent 25 or 35 minutes of ischemia followed by 60 minutes of reperfusion.
- Mitochondrial function (oxidative phosphorylation, calcium retention) and cardiac function (developed pressure, inotropy, lusitropy) were assessed.
Main Results:
- DCD hearts exhibited progressive impairment in oxidative phosphorylation and calcium retention capacity post-ischemia compared to CBD hearts.
- Reperfusion exacerbated mitochondrial dysfunction in DCD hearts.
- Significant reductions in developed pressure, inotropy, and lusitropy were observed in DCD hearts.
Conclusions:
- Ischemia and reperfusion significantly damage mitochondria and impair cardiac function in DCD hearts.
- Targeted interventions before ischemia and during reperfusion may protect mitochondria.
- Protecting mitochondria could enhance the suitability of DCD hearts for transplantation.
Abstract:
The ultimate treatment for patients with end-stage heart failure is heart transplantation. The number of donor hearts which are primarily procured from donation after brain death (DBD) donors is limited, but donation after circulatory death (DCD) donor hearts can increase the heart donor pool. However, ischemia and reperfusion injuries associated with the DCD process causes myocardial damage, limiting the use of DCD hearts in transplantation. Addressing this problem is critical in the exploration of DCD hearts as suitable donor hearts for transplantation. In this study, rat hearts were procured following the control beating-heart donor (CBD) or DCD donation process. Changes in mitochondria and cardiac function from DCD hearts subjected to 25 or 35 minutes of ischemia followed by 60 minutes of reperfusion were compared to CBD hearts. Following ischemia, rates of oxidative phosphorylation and calcium retention capacity were progressively impaired in DCD hearts compared to CBD hearts. Reperfusion caused additional mitochondrial dysfunction in DCD hearts. Developed pressure, inotropy and lusitropy, were significantly reduced in DCD hearts compared to CBD hearts. We, therefore, suggest that interventional strategies targeted before the onset of ischemia and at reperfusion could protect mitochondria, thus potentially making DCD hearts suitable for heart transplantation.
