CARDIAC TOLERANCE TO ISCHEMIA: DEVELOPMENTAL AND SEX DIFFERENCES

Age and sex play essential role in the cardiac tolerance to ischemia/reperfusion (I/R) injury: cardiac resistance significantly decreases during postnatal maturation and female heart is more tolerant as compared with the male myocardium (1). The mechanisms of the high tolerance of the neonatal and female hearts have not yet been satisfactorily clarified. Some recent data indicate that mitochondria could play an important role in this effect. It is widely accepted that mitochondrial dysfunction and particularly mitochondrial permeability transition pore (MPTP) opening plays a major role in determining the extent of cardiac I/R injury. We have observed that the MPTP sensitivity to the calcium load differs in mitochondria isolated from neonatal and adult myocardium as well as from adult male and female hearts. Neonatal and female mitochondria are more resistant both in the extent and in the rate of mitochondrial swelling induced by high calcium concentration. Our data further suggest that age- and sex-dependent specificity of the MPTP is not the result of different amounts of ATP synthase and cyclophilin D (CypD): neonatal and adult hearts, similarly as the male and female hearts contain comparable amount of MPTP and its regulatory protein CypD (2,3) . We can speculate that the lower sensitivity of MPTP to the calcium induced swelling may be related to the higher ischemic tolerance of both neonatal and female myocardium (4).

Key words: Neonatal heart, Female heart, Ischemia/reperfusion injury, Cardiac ischemic tolerance, Mitochondrial permeability transition pore