Maja Brøgger Thomassen, Klaes Vincent Lenbroch, Johanne Gade Lilleøre, Shan Awzhin Ali, Niels Moeslund, Per Lehnert, Mats Bue, Maiken Stilling, Roni Ranghøj Nielsen, Tor Skibsted Clemmensen, Hans Eiskjær
Intramyocardial microdialysis is a feasible method for real-time assessment of myocardial metabolism during DCD heart transplantation. DCD transplantation is characterized by dynamic phase-specific metabolic alterations, with the L/P ratio serving as a sensitive marker of ischemic stress and mitochondrial dysfunction.
BACKGROUND: Myocardial metabolism during donation after circulatory death (DCD) heart transplantation remains poorly characterized. This study investigated the feasibility of intramyocardial microdialysis for real-time metabolic monitoring and characterized changes in ischemic metabolites and mitochondrial function throughout the transplantation sequence.
METHODS: Danish Female Landrace pigs (76-85 kg) were used for six orthotopic DCD heart transplantations. Donor hearts underwent 10 min of asystolic warm ischemia followed by normothermic regional perfusion (NRP), procurement, and static cold storage (SCS). Microdialysis catheters were placed in both ventricles for continuous measurement of glucose, lactate, pyruvate, and glycerol. Serial myocardial biopsies were analyzed by high-resolution respirometry for assessment of mitochondrial function. After implantation, grafts were reperfused and assessed by invasive hemodynamic measurements.
RESULTS: Intramyocardial microdialysis was feasible and identified four distinct metabolic phases. The lactate-to-pyruvate (L/P) ratio increased during the first phase of circulatory arrest, partially normalized during the second phase of NRP, increased again during SCS and implantation in the third phase, and declined following reperfusion in the fourth phase. The highest L/P ratios were observed during implantation. The right ventricle (RV) exhibited a significantly greater L/P ratio than the left ventricle. Peak RV L/P ratio was associated with elevated post-transplant central venous pressure and inversely correlated with mitochondrial oxidative phosphorylation capacity following NRP.
CONCLUSION: Intramyocardial microdialysis is a feasible method for real-time assessment of myocardial metabolism during DCD heart transplantation. DCD transplantation is characterized by dynamic phase-specific metabolic alterations, with the L/P ratio serving as a sensitive marker of ischemic stress and mitochondrial dysfunction.