Abstract Fri135: Metabolic Adaptations after Myocardial Ischemia in Adult Spiny Mouse ( Acomys)

Background: Ischemic cardiomyopathy is caused by inadequate blood supply, leading to heart failure through cell death and metabolic disruption. Unlike most organs, adult heart tissue cannot regenerate. The Acomys mouse, however, shows healing abilities and maintains better heart function after myocardial infarction than typical laboratory mice (C57BL/6 Mus ). This study compares the metabolic profiles of Acomys and Mus to identify mechanisms of Acomys cardiac resilience to injury. Methods/Approach: Myocardial infarction (MI) in Acomys and the Mus was induced by LAD ligation. We conducted metabolomic analysis on heart tissue from sham and MI animals (day 1, 3, and 7 post MI). Oxygen consumption rate of isolated cardiomyocytes from both species was quantified using the Seahorse system. Results/Data: Following MI, Acomys mice demonstrate metabolic advantages over Mus mice. While both species show increased amino acid metabolism after MI, this change is more dramatic in Mus . Acomys exhibit stronger upregulation of several key metabolic pathways post MI, including the pentose phosphate pathway (PPP), glycolysis gluconeogenesis, purine metabolism, and pentose glucuronate interconversions. Despite having a higher baseline metabolic rate but lower reserve capacity, Acomys experience smaller decreases in basal respiration and ATP production after MI, indicating better preservation of metabolic. In contrast, Mus show greater increases in non-mitochondrial oxygen consumption following MI, suggesting a more pronounced oxidative stress response. Conclusion: The metabolic adaptations in Acomys , characterized by enhanced glycolysis, activation of the PPP, and improved antioxidant capacity, likely contribute to their cardiac resilience and recovery following MI. This metabolic profile allows Acomys to better manage energy demands and oxidative stress during cardiac injury, potentially supporting the enhanced survival capacity of cardiomyocytes.