Abstract
Development of hibernation strategies for cold preservation of human organs represents a far-reaching goal in transplantation surgery. Short cold storage times of <6 h tolerated by the human heart remain a major clinical problem. Mitochondrial cold storagereperfusion injury is becoming recognized as a limiting factor in preservation of organs from non-hibernating mammals. Damaged mitochondria lead to cellular injury by reduction of ATP supply, oxidative stress, disturbance of ion balance, cytochrome c release and induction of apoptosis and necrosis. Profiles of mitochondrial injuries differed after (1) cold preservation of isolated rat heart mitochondria, (2) cold preservation of the rat heart, and (3) after transplantation and rewarming/reperfusion. Importantly, a specific defect of complex I of the electron transport chain, uncoupling of oxidative phosphorylation and the pronounced release of cytochromec from mitochondria were absent after cold storage but developed during reperfusion, in proportion to the loss of heart function. Cold preservation of isolated heart mitochondria could be significantly prolonged by a mitochondrial preservation solution containing antioxidants, mitochondrial substrates, ATP, histidine, and oncotic agents. Successful cold storage of heart mitochondria demonstrates a large scope for improvement of heart preservation solutions. In this context, comparison of intracellular conditions and cold ischemia-reperfusion injury in hibernating and non-hibernating mammals may provide a rationale for improvement of clinical organ hibernation strategies.
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Gnaiger, E. et al. (2000). Mitochondria in the Cold. In: Heldmaier, G., Klingenspor, M. (eds) Life in the Cold. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-04162-8_45
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DOI: https://doi.org/10.1007/978-3-662-04162-8_45
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