A Rodent Model of Cardiac Donation After Circulatory Death and Novel Biomarkers of Cardiac Viability During Ex Vivo Heart Perfusion

Transplantation
Mark J KearnsJohn H Boyd

Abstract

Organ donation after circulatory death (DCD) is increasingly being used as a means of addressing the organ supply/demand mismatch in solid organ transplantation. There is reluctance to use DCD hearts, due to an inability to precisely identify hearts that have suffered irreversible injury. We investigated novel biomarkers and clinically relevant endpoints across a spectrum of warm ischemic times, before and during ex vivo heart perfusion (EVHP), to identify features associated with a nonviable cardiac phenotype. Donor rats sustained a hypoxic cardiac arrest, followed by variable acirculatory standoff periods (DCD groups). Left ventricular function, histochemical injury, and differences in left ventricular gene expression were studied before, and during, EVHP. As warm ischemic time exposure increased in DCD groups, fewer hearts were functional during EVHP, and ventricular function was increasingly impaired. Histochemical assessment identified severely injured hearts during EVHP. A novel gene expression signature identified severely injured hearts during EVHP (upregulation of c-Jun, 3.19 (2.84-3.60); P = 0.0014; HMOX-1, 3.87 (2.72-5.50); P = 0.0037; and Hsp90, 7.66 (6.32-9.27); P < 0.0001 in DCD20), and may be useful in identifyin...Continue Reading

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Citations

May 18, 2017·Transplantation·Peter S Macdonald
May 20, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Michael MengelRobert B Colvin
Apr 19, 2019·Circulation. Heart Failure·Petra NiederbergerSarah L Longnus
Mar 10, 2020·Transplantation·Giosafat Spitaleri, Marta Farrero
Feb 2, 2021·Frontiers in Cardiovascular Medicine·Maria ArnoldSarah Longnus
Jan 24, 2021·Clinical Transplantation·Giosafat SpitaleriMarta Farrero
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May 2, 2020·The Journal of Thoracic and Cardiovascular Surgery·Henry AcerosNicolas Noiseux
Nov 20, 2020·Transplantation·Laura Anguela-CalvetEva Oliver-Juan
May 11, 2020·The Journal of Thoracic and Cardiovascular Surgery·David J Chambers

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