Learning from the kidney: improving heart recovery from hypothermia

Extending donor organ preservation times would substantially improve patient outcomes by widening safety margins and enabling better donor-to-patient matching. While clinical 4°C static storage typically preserves donor kidneys for 18–24 h, donor hearts are limited to ∼4 h. This clinical disparity is traditionally attributed to the higher baseline metabolic demand of cardiac tissue. This narrative review challenges this conventional assumption by comparing the distinct metabolic profiles of the heart and kidney at both 37°C and 4°C. We propose two mechanisms to explain how kidneys maintain robust functional recovery despite a much steeper decline in ATP concentration during hypothermic storage: (1) a significantly higher ATP consumption rate in hypothermic kidneys compared to hearts, and (2) a lower susceptibility to and degree of cold-induced tissue acidosis in the kidney. Building on these pathways, we outline targeted therapeutic interventions, such as inhibition of the Na + /H + -exchanger, to mitigate downstream sodium and calcium overload in cardiac tissue. Finally, we advance acidosis as a salient concern in organ cryopreservation, offering a fresh mechanistic framework (the acidosis hypothesis) to alleviate non-specific cryoprotective agent (CPA) toxicity and enhance heart tolerance during hypothermic CPA exposure.