Drp1-Dependent Mitochondrial Fission Contributes to Lactic Acid-Induced Chicken Cardiomyocyte Damage

Enhanced glycolysis and elevated lactic acid (LA) production are observed during sudden death syndrome (SDS) in broilers. However, the mechanism underlying LA-induced cardiomyocyte damage and heart failure in fast-growing broilers remains unclear. In this study, chicken embryo cardiomyocytes (CECs) were cultured and treated with LA to investigate LA-induced CEC injury and its mechanism, aiming to develop strategies to prevent LA-induced SDS in broilers. Results showed that LA inhibited CEC proliferation and contraction whereas inducing apoptosis. Furthermore, LA disrupted mitochondrial ultrastructure, reduced mitochondrial membrane potential, activated mitophagy, and disturbed mitochondrial dynamics. Treatment with Mdivi-1, a selective Drp1 inhibitor, improved CEC viability, restored mitochondrial network integrity, reduced reactive oxygen species production, and inhibited LA-induced apoptosis. These findings suggest that LA-induced cardiomyocyte injury during SDS in broilers is associated with mitochondrial damage and increased mitochondrial fission. The inhibition of mitochondrial hyperfission by Mdivi-1 effectively preserves CEC morphology, structure, and function, playing a critical role in preventing LA-induced damage. This study provides a foundation for strategies to prevent and control SDS in broilers.