Metabolic adaptations in the hypothermic myocardium: Mechanisms and clinical implications

Hypothermia is widely used in clinical practice for myocardial protection during cardiac arrest (CA), surgery, and organ preservation. However, a comprehensive understanding of how hypothermia reshapes myocardial metabolism remains lacking. This review summarizes current knowledge on how hypothermia affects myocardial substrate utilization and mitochondrial function. Under hypothermia conditions, the heart exhibits profound metabolic remodeling characterized by impaired fatty acid uptake and oxidation, restricted glucose transport, enhanced lactate production, and increased reliance on ketone bodies. Mitochondria exhibit altered oxidative phosphorylation (OXPHOS) efficiency, electron transport chain (ETC) activity, morphology and mitochondrial quality control (MQC) network. Rewarming poses a critical metabolic challenge, characterized by delayed recovery from calcium dysregulation and metabolic mismatch that contribute to cardiac dysfunction, necessitating controlled slow rewarming and metabolic modulatory interventions. Notably, metabolic responses to hypothermia are context-dependent, varying with temperature depth, patient age/sex, and injury type. Advanced metabolic imaging techniques enable non-invasive monitoring of myocardial energetics, facilitating personalized temperature management. In conclusion, decoding the metabolic logic of hypothermia-induced myocardial reprogramming provides a foundational framework for optimizing therapeutic hypothermia (TH)-based therapies. Future research should focus on defining gradient-dependent metabolic responses, integrating multi-omics approaches, and exploring metabolic-immune crosstalk to refine precision-guided strategies in cardiovascular medicine.