The main cause of the heart function instability with age is mitochondrial dysfunction. On the Langendorf's isolated Wistar rat heart was shown that old rat heart (24–26 months) characterized by the loss of ischemic tolerance which consist in more pronounced drop of P_LV and dP/dt max and dP/dt min during 40-min reperfusion after 30-min ischemia compared to adult hearts (5-6 months). It was accompanied by the increased m-RNA proapoptotic bax expression, increased mitochondrial permeability and sensitivity of the MPTP-opening to Ca²⁺ and oxidants in mitochondria isolated from old rat heart as compare to adult animals. Increased sensitivity partially arise from the reduction of NO- content due to half decreasing in activity of the constitutive NO-synthase and entails with increased content of H₂O₂, superoxide anion and dien conjugates in old rat heart mitochondria. Course intraperitoneal injection of the hormone of pineal gland melatonin (14 days, 1,5 mg/kg) to old rats rehabilitated ischemic tolerance of isolated heart, decreased sensitivity of the MPTP-opening to Ca²⁺ and m-RNA bax expression in rat heart.