MP-5 - EVALUATING THE IMPACT OF EXTENDED WARM ISCHEMIC TIME USING EX-VIVO HEART PERFUSION IN JUVENILE PORCINE MODELS OF CIRCULATORY DEATH

Background: In heart transplant (HT), the demand for donor hearts exceeds supply. This issue is critical in the pediatric population, where rate of waitlist mortality or waitlist withdrawal due to clinical deterioration doubles that of adults. Donation after circulatory death (DCD) is one strategy to expanding the donor pool and shown to increase HT rate by 15-30%. DCD hearts are considered high-risk allografts due to the injury sustained from warm ischemia time (WIT). Hearts with a functional WIT >30 minutes are abandoned due to concern for irreversible damage from ischemia and ischemia/reperfusion injury. This threshold is particularly limiting for pediatric hearts that take longer to arrest, compared to adult hearts. Ex-vivo heart perfusion (EVHP) is a technique to rehabilitate and assess marginal donor hearts prior to HT. The aim of the study is to apply EVHP to recover and appraise juvenile DCD hearts subjected to WIT of 30, 45, and 60min.

METHODS AND RESULTS: Juvenile porcine DCD hearts subjected to different WITs are reperfused for 2hr (perfusion mode, PM) at 10ml/kg/min, then reanimated using the EVHP’s working mode (WM) for 2hr functional assessment (Figure 1). In WM, EVHP flows were gradually uptitrated up to 120% of full cardiac output (CO) estimated by 100ml/kg/min, within the physiological limits of left atrial pressure < 10 mmHg. Preliminary data of the 7 animals (n=3 in 30min, n = 3 in 45min, and n = 1 in 60min WIT) showed positive trend between myocardial edema with increasing WIT: mean % heart weight gained pre/post- EVHP of 17.3 ± 16, 30.3 ± 20, and 44.4 %, respectively. Throughout EVHP, arterial lactate uptrended similarly in all WIT groups: 3.9 ± 1.1, 5.6 ± 1.5, and 7.6 ± 1.3 mmol/L at start of reperfusion, after 2h PM, and after 2h WM, respectively. Left ventricular pressure-volume loop measurements of maximum and mininum dP/dT showed improvement of both systolic and diastolic function through reperfusion, with greatest recovery of diastolic function seen in the 30min WIT group and poorest in 60min WIT group (Figure 2). 30, 45, 60min WIT groups achieved 118 ± 1.7, 46 ± 7, and 14% of full CO, respectively.


Conclusion: EVHP improves function of DCD hearts but is unable to achieve full recovery of cardiac function for 45 and 60min WIT. Clarifying the WIT threshold in the pediatric population and the role of EVHP facilitates the arrival of DCD HT in Canada.