*Purpose: Prior studies using Steen’s cold perfusion storage technique for heart ischemia minimization (IM) prevented initial xenograft dysfunction (IXD). Our pilot data evaluates the effect of IM on cardiac injury and function during subsequent ex vivo xenoperfusion of wild-type (WT) and quadruple knock-out (QKO) porcine hearts.

*Methods: Hearts from pigs with knockout of growth hormone receptor and the three principal antigens causing antibody-mediated graft injury (QKO) were compared to WT hearts on an ex vivo perfusion circuit. Three QKO and 1 WT hearts were perfused with a cold Steen solution for 2.5h after procurement (IM); 2 QKO and 2 WT hearts were cold-stored in iced saline for 2.5h (CS). Cardiac function was assessed in working heart mode (WHM) during subsequent perfusion with fresh human blood.

*Results: Both WT CS hearts did not generate forward flow in WHM; 1 WT IM heart had declining function and failed at 3h (Fig.2F). Troponin levels increased throughout ex vivo perfusion in both QKO and WT groups, however troponin elaboration (as mean final troponin, ng/mL) was significantly attenuated with IM compared to CS for WT (IM 185, CS>1000; p=0.02) but not QKO hearts (IM 750, CS>1000; p=0.37)(Fig.1). Cardiac function (as increase in cardiac output with increased LA pressure) was relatively preserved over 4h in 2/3 QKO IM hearts (Fig2A,B) and 1/2 QKO CS hearts (2E), while 3/3 WT hearts (2 with CS; 1 with IM, 2F) and 2/5 QKO hearts (1 with IM, 2C; 1 with CS, 2D) failed within 4h. In this pilot series, IM did not significantly improve survival to 4h.

*Conclusions: IM with cold Steen solution appears to protect WT hearts from IXD, with a trend toward reduced cardiac injury (as troponin release) during subsequent perfusion with human blood for both WT and QKO hearts. While preliminary, these observations support prior demonstrations of the effectiveness of IM to prevent IXD in orthotopic cardiac xenotransplantation. The incomplete physiologic protection and residual troponin release seen in QKO hearts despite IM indicates the need to address other mechanisms of graft injury such as complement, coagulation, and adhesive interactions.

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