Background: Ex vivo heart perfusion (EVHP) of donation after circulatory death (DCD) hearts has become an effective strategy in adults, however small circulating volume in pediatrics poses a challenge of low-hemoglobin (Hb) perfusate. We sought to evaluate the impact of Hb level during EVHP on DCD hearts using a juvenile porcine model.
METHODS AND Results: Sixteen DCD piglet hearts (11-14 kg) were reperfused with non-working mode (NWM) for 4 hours followed by working mode (WM). Metabolism, cardiac function and cell damage were compared between two groups: Low-Hb (Hb, 5.0–5.9 g/dl; n = 8) and Normal-Hb group (Hb, 7.5–8.4 g/dl; n = 8). Between-group differences were evaluated using two-sample t-tests or Fisher's exact tests. Although perfusion flow of 10 ml/kg/min was consistent in each group, the coronary vascular resistance was lower in Low-Hb group (P = 0.014, respectively). As the overall between-group differences, myocardial oxygen consumption was lower, and arterial and venous lactate level were higher in Low-Hb group during NWM (P < 0.001, P = 0.001, P < 0.001, respectively). The maximum rate of pressure change (dP/dt max) during NWM was lower in Low-Hb group (P < 0.001), while the minimum rate of pressure change (dP/dt min) did not differ between the two (P = 0.22). During WM, Low-Hb group demonstrated worse cardiac function in all variables: decreased dP/dt max and dP/dt min, lower cardiac output and higher left atrial pressure. (P < 0.05 for all). The percentage gain in the heart weight before and after EVHP did not differ significantly between the groups. (P = 0.77).
Cardiac troponin-I (cTnI) concentration increased during EVHP in both groups. Adjusted cTnI at T3 did not differ significantly (P = 0.152). In western blots analyses, endothelial nitric oxide synthase (eNOS) and phospho-eNOS (p-eNOS) were higher in Low-Hb group (P = 0.046, P = 0.007, respectively). No differences were found in p-eNOS/eNOS and cleaved caspase-3 between the groups (P = 0.199, P = 0.159, respectively). In histological analysis, myocardial contraction bands, hemorrhage and neutrophils were more observed in Low-Hb group (P < 0.05 for all). Overall myocardial injury score was higher in Low-Hb group (P = 0.028).
Conclusion: Low-Hb perfusate with inadequate oxygen delivery expedited anaerobic metabolism, which resulted in a suboptimal DCD heart recovery and reduced cardiac function. Preparing optimal perfusate is a key element to organ protection, and further efforts to refine the priming volume of EVHP or transfusion strategy are required.
