Abstract

Introduction: The utilization of extracorporeal membrane oxygenation (ECMO) for Donation after Circulatory Death (DCD) can substantially increase the donor pool, organ yield per donor, and organ shelf life. Clinical attempts to recover organs for transplantation after uncontrolled DCD are very complex and hard to reproduce. As a preliminary strategy for completing this endeavor, experimental protocols employing feasible animal models are strongly recommended. Hypothesis: The objective of the investigation was to develop a mouse model of ECMO-based cadaver management protocol for uncontrolled DCD donation after "out-of-hospital" death. Methods: Following 10 min after confirmed death, murine cadavers (C57BL/6 background) were administered with heparin-streptokinase and cannulated for veno-arterial ECMO. Cadaver bodies were connected to a murine ECMO machine 1 h post-mortem and subjected to extracorporeal circulation for subsequent 2 hrs. Blood gas parameters, cardiac activity, and general organ state were assessed using BGA analysis, ECG, and histology, accordingly. We have designed and incorporated into an ECMO circuit a previously unreported, miniaturized murine hemodialysis for the treatment of severe hyperkalemia and metabolic acidosis that arose following death. Results: Control BGA parameters recorded 1 h after death were incompatible with normal physiology: extremely low blood pH, profound negative base excess, and extraordinarily high lactate and K + levels. Two hours after ECMO support, blood pH values of a cadaver body restored from <6.5 to 7.3 ± 0.05, pCO 2 was lowered from >130 to 41.7 ± 10.5 mmHg, sO2, base excess, and HCO 3 were all elevated from below detection thresholds to 99.5 ± 0.6%, -4 ± 6.2 and 22.0 ± 6.0 mmol/L, respectively (Student T-test, p < 0.05). The implementation of hemodialysis resulted in a significant decrease in both hyperlactatemia and hyperkalemia. Conclusions: Our model presents novel opportunities for the management of cadaver organs in order to promote uncontrolled DCD donation, thereby contributing to the resolution of the organ shortage problem. Our approach enables the implementation of a variety of modern blood purification techniques in cadaveric organ recovery using ECLS.

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