A RODENT MODEL OF CARDIAC DONATION AFTER CIRCULATORY DEATH AND NOVEL BIOMARKERS OF CARDIAC VIABILITY DURING EX VIVO HEART PERFUSION.

Background: 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 (WITs), prior to and during ex vivo heart perfusion (EVHP), to identify features associated with a non-viable cardiac phenotype. Methods: 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 prior to, and during, EVHP. Results: As WIT 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

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