Hypothermic Ex Vivo Perfusion of Brain Dead Donor Hearts Improves Survival, Systemic Inflammation and Cardiac Function Following Heart Transplantation

Introduction: Hypothermic ex vivo perfusion (HEVP) of donor hearts for transplantation (HTx) may provide superior preservation to cold static storage (CSS). Extended donor heart ischemic time increases the risk of primary graft dysfunction and decreases patient survival. We examined post-HTx survival, systemic inflammation and cardiac function following donor heart preservation by HEVP. Methods: Brain death (BD) was induced in donor sheep for 24 hours. Donor hearts were preserved by a) CSS for 2 hours (n=7), b) HEVP for 2 hours (n=4), or c) HEVP for 8 hours (n=4). Orthotopic HTx was performed in matched re- cipients. Recipients were weaned from cardiopulmonary bypass and monitored for 6 hours. Recipient blood was collected and assayed for inflammatory cytokines and car- diac markers. Cardiac function was assessed by echocardiography. Results: Compared to CSS, HEVP improved post-HTx recipient survival out to 6 hours (73% vs 100%) and reduced systemic IL-6 (6 hrs–CSS: 120,380673,494; 2hr HEVP: 14,05166,796; 8hr HEVP: 23,196610,438 pg/mL) and IL-8 (6 hrs–CSS: 10816187; 2hr HEVP: 241630; 8hr HEVP: 3846192 pg/mL) levels in recipients. Post-HTx function was no different between groups, but HEVP reduced the require- ment for vasoactive support compared to CSS. Post-HTx cardiac function was no different between groups, and troponin levels were reduced with 2 hours HEVP. Conclusion: We successfully extended preservation time for BD donor hearts to 8 hours using HEVP, without compromising post-HTx recipient function. HEVP improved early post-HTx survival, and reduced systemic inflamma- tion. The use of HEVP may assist in overcoming limitations in preservation time associated with HTx.