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INSTITUTE OF PHYSIOLOGY CAS

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Developmental aspects of cardiac ischemic tolerance


The immature heart is highly tolerant to ischemic injury, but chronic oxygen deficit during early ontogeny may have negative consequences that persist till adulthood. We study mechanisms responsible for developmental changes of cardiac ischemic tolerance.

Cardiac ischemic tolerance during postnatal ontogeny

Cardiac tolerance of the immature heart to acute oxygen deficiency is significantly higher as compared with the adult myocardium. The developmental changes are sex-dependent: cardiac tolerance is similar in males and females up to the end of the weaning period; the adult female heart is, however, significantly more resistant to oxygen deprivation than the male heart. The mechanisms of the higher resistance of the neonatal heart to oxygen deprivation have not yet been satisfactorily clarified. In this connection the question arises on the role of mitochondria in view of the fact that mitochondria are responsible for cellular oxygen handling. Our results have revealed that mitochondria isolated from the immature heart are more tolerant to ischemic injury; the questions remains, whether the tolerance of cardiac mitochondria to oxygen deprivation is sex-dependent.   

 

Impact of perinatal hypoxia on cardiac tolerance to ischemia in adults

Human epidemiological studies have shown a clear association of adverse perinatal hypoxic environment and increased risk of ischemic heart disease in later adult life. Experimental studies on late effects of hypoxia have confirmed the clinical data: the cardiac muscle of males exposed perinatally to chronic hypoxia is significantly less tolerant to ischemic injury as compared with control animals. We have observed in the rat model that late myocardial effects of hypoxemia, experienced in early life, may be sex dependent: whereas the male myocardium is significantly less tolerant, the heart muscle of females exposed perinatally to hypoxic deprivation is more resistant to ischemic injury as compared with controls.

 

Clinical importance of developmental approach

The importance of developmental approach for experimental and clinical cardiology is indisputable. It offers new possibilities in studies of pathogenesis, prevention and therapy of serious cardiovascular diseases. Retrieval of developmental mechanisms participating on changes in cardiac tolerance to hypoxia is the best example for this view. The experimental results may be utilized in the clinical practice, particularly in pediatric cardiology and cardiac surgery.