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Canadian Journal of Cardiology

LARGE ANIMAL MODEL OF DONATION AFTER CIRCULATORY DEATH AND NORMOTHERMIC REGIONAL PERFUSION FOR CARDIAC ASSESSMENT

      Background

      The increase in demand for cardiac transplantation throughout the years has fueled interest in donation after circulatory death (DCD) to expand the organ donor pool. However, the DCD process is associated with the risk of cardiac tissue injury due to the inevitable period of warm ischemia. Normothermic regional perfusion (NRP) allows for an in-situ organ assessment, allowing the procurement of hearts determined to be viable.

      Methods and Results

      Here, we described a clinically relevant large animal model of DCD followed by NRP. Circulatory death was established in anesthetized pigs by stopping mechanical ventilation. After a preset warm ischemia period, an extracorporeal membrane oxygenator (ECMO) was used for a NRP period lasting at least 30 min. During this reperfusion period, the model allowed the collection of various myocardial biopsies and blood samples for initial cardiac evaluation. Once NRP was weaned, biochemical, hemodynamic, and echocardiographic assessments of cardiac function and metabolism were performed before organ procurement. DCD hearts initially reperfused with NRP demonstrated similar functional recovery following transplantation when compared to conventional beating heart donation preserved with cold storage. Following DCD, there is a severe decline in cardiac index, however, these organs demonstrated similar functional recovery post-transplantation when compared to conventionally transplanted hearts (beating heart donation followed by cold storage). Cerebral oximetry measurements dropped significantly after the withdrawal of life-sustaining treatments and remained stable throughout the NRP procedure. This confirmed the absence of adequate cerebral perfusion during NRP when the supra-aortic vessels were clamped. Lung compliance measurements throughout the experiments showed no significant changes from baseline during the NRP procedure.

      Conclusion

      This large animal model of DCD followed by thoracoabdominal NRP can be a reliable method to assess the cardiac function of a donor heart within the donor and establish if the organ can be transplanted. This protocol closely simulates the clinical scenario previously described for DCD and NRP in heart transplantation and has the potential to facilitate studies aimed at decreasing ischemia-reperfusion injury and enhancing cardiac functional preservation and recovery. It has the potential of being an adequate pre-clinical model that can be used to investigate novel pharmacologic and non-pharmacologic interventions that might improve cardiac functional recovery and have been previously validated only in small-animal models.