Crystalloid Custodiol based ex vivo perfusion demonstrates comparable efficacy to blood perfusion in a clinically relevant DCD heart transplantation large animal model
T Balint, K Benke, G Damenija Jr, M Csonka, S Spiesshofer, B A Barta, L Saemann, B Merkely, M Ruppert, G Szabo, T RadovitsAbstract
Introduction
Donation after circulatory death (DCD) has the potential to increase the number of available donor hearts by approximately 30%. During DCD procedures, ex vivo machine perfusion (EVMP) is applied to protect the graft from ischemic injury. Although blood-based EVMP is currently the clinically established approach, crystalloid preservation solutions—long used in static cold storage—have shown promising results in several preclinical EVMP models. However, further experimental evidence is required to assess their applicability.
Purpose
The aim of this study was to compare oxygenated crystalloid EVMP using Custodiol-HTK with oxygenated donor blood EVMP in a preclinical canine DCD heart transplantation model.
Methods
Sixteen orthotopic heart transplantations were performed using 32 dogs in donor–recipient pairs. Under general anaesthesia and mechanical ventilation, circulatory arrest was achieved by ventilatory withdrawal, followed by a 10-minute warm ischemic period. After explantation, donor hearts underwent four hours of EVMP according to two different protocols: hypothermic perfusion with oxygenated Custodiol-HTK solution or normothermic perfusion with oxygenated donor blood. Orthotopic transplantation was subsequently performed. Graft function and transplant success were assessed using invasive pressure–volume analysis (PRSW, ESPVR, EDPVR, Tau, dp/dtmin) and serum biomarkers (troponin I, TNFα, IL-6). Measurements were obtained at baseline (donor and recipient, respectively) and at 60 (RP60) and 120 minutes (RP120) after reperfusion.
Results
No significant differences were observed between Custodiol-HTK and blood-based perfusion in either systolic (e.g., ESPVR at RP120: 2.42 ± 1.50 vs. 2.37 ± 1.56 mmHg/mL, p = 0.916) or diastolic cardiac function (e.g., EDPVR at RP120: 5.13 ± 3.37 vs. 3.11 ± 2.29 mmHg/mL, p = 0.259). Serum biomarker levels were also comparable between groups (e.g., IL-6 at RP120: 2842 [1177–6935] vs. 3051 [1998–3939] pg/mL, p = 0.878).
Conclusions
In this experimental DCD heart transplantation model, hypothermic EVMP using oxygenated Custodiol-HTK was non-inferior to normothermic oxygenated blood-based EVMP. Crystalloid perfusion may represent a safe and practical alternative for ex vivo heart preservation in DCD transplantation.