OBJECTIVES: This study investigated the mechanisms underlying myocardial damage after perinatal hypoxia. METHODS: An intrauterine hypoxia-ischemia model (I/U HI) and a hypoxia/reoxygenation (H/R) model were established. Myocardial damage, mitochondrial function, and mitochondria permeability transition pore (MPTP) opening were determined. The results, presented as means ± SD, were analyzed using SPSS. RESULTS: Intrauterine hypoxia induced cardiac damage, mitochondrial dysfunction, and MPTP opening in neonatal rats. H/R led to apoptosis and MPTP opening. cTnI and apoptosis-inducing factor (AIF) levels were positively correlated with the degree of MPTP opening. The larger degree of MPTP opening combined with the significant increases in the Ca CONCLUSIONS: Increased MPTP opening may play a crucial role in perinatal asphyxia-induced myocardial damage in neonatal rats.