Development of myocardial tolerance to oxygen deficiency - Experimental aspects

Abstract

The current interest in the hypoxic immature myocardium is due primarily to clinical need as hypoxic congenital heart disease continues to be the leading single cause of death from congenital heart disease and coronary disease is no longer a disease of the fifth and higher decades but its risk factors start appearing already in the early stages of ontogenic development. Moreover, the number of patients undergoing successful surgery for cyanotic congenital heart disease in the early stage of ontogenic development in our adult population continues to grow. These individuals are nearing an age whereby the risk of serious cardiovascular disease, and coronary heart disease in particular, increases. Experimental studies show that the immature heart is more tolerant to acute oxygen deficiency than the adult heart. While the reasons underlying this difference are unclear yet, it is most likely that contributing factors include developmental changes of energy metabolism including mitochondrial function. The high tolerance of the neonatal heart cannot be further enhanced by ischemic preconditioning or adaptation to chronic hypoxia; endogenous protective mechanisms do not set in until tolerance starts to decline in the course of development. Tolerance of the adult myocardium to acute oxygen deficiency may be significantly affected by perinatal hypoxia. The above results show that the developmental approach offers new possibilities in the study of the pathogenesis, prevention and treatment of serious cardiovascular disease.