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β-hydroxybutyrate is a molecule synthesized in the liver that can be used as an alternative to glucose in cellular metabolism. BHB metabolism does not produce lactic acidosis which makes it an optimal source of energy for tissues in an ischemic state. Melatonin is a hormone produced in the pineal gland that aids in slowing the metabolic rate. Both BHB and Melatonin have antioxidant properties that assist in relieving oxidative stress due to an increased metabolic rate during post-ischemic reperfusion.
Testing consisted of infusing donor pigs with either BHB/M or a vehicle control. The pigs were then made brain-dead and their hearts were harvested under standard conditions and placed in a UW solution or a UW+BHB/M solution under static cold conditions. Tissue samples were then analyzed immediately after harvest, 2 days, and 8 days post-harvest using a Seahorse XFe96 Flux Analyzer. This test analyzed the oxygen consumption rate in order to show mitochondrial function.
We hypothesize that the BHB/M solution will aid in mitochondrial function while the tissues are in an ischemic state. We believe this will prolong the viability of harvested organs in order to increase the amount of available organs for transplantation. We also believe that future testing will show that the BHB/M will relieve the effects of oxidative stress during reperfusion of the tissues which will decrease the risk or organ failure post-transplantation.
β-hydroxybutyrate, Melatonin, Metabolism, Oxygen Consumption Rate, BHB/M, Mitochondria
Johnson, Ryan; Urban, Marian; Merani, Shaheed; and Trease, Andrew, "Analyzing Mitochondrial Bioenergetics to Improve Organ Hibernation Methods." (2023). Posters: 2023 Summer Undergraduate Research Program. 6.