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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.
Highlights
Heart Failure (HF) affects 6 million adults in the United States [1]
To determine the effect of Donation after circulatory death (DCD) induced ischemia on oxidative phosphorylation (OXPHOS), we measured the rate of oxygen consumption in the two mitochondrial populations, subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM), from hearts subjected to 25 minutes or 35 minutes of ischemia (Fig 1)
Compared to control beating-heart donor (CBD) hearts, the rate of ADPstimulated OXPHOS was decreased by 42% and 46% in SSM from DCD hearts with 25 minutes and 35 minutes of ischemia respectively when glutamate was used as complex I substrate (Fig 2A)
Summary
Heart Failure (HF) affects 6 million adults in the United States [1]. Patients with end-stage HF require heart transplantation (HTx) to improve survival [2]. Most transplantable hearts come from donation after brain death (DBD) donors [3]. The availability of these donors is limited [3, 4]. Donation after circulatory death (DCD) donors can expand the heart donor pool. In DCD donors, organs are procured following death pronouncement based
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