Development of cardiac sensitivity to oxygen deficiency: Comparative and ontogenetic aspects

Hypoxic states of the cardiovascular system are undoubtedly associated with the most frequent diseases of modern times. They originate as a result of disproportion between the amount of oxygen supplied to the cardiac cell and the amount actually required by the cell. The degree of hypoxic injury dep ends not only on the intensity and duration of the hypoxic stimulus, but al so on the level of cardiac tolerance to oxygen deprivation. This variable c hanges significantly during phylogenetic and ontogenetic development. The h eart of an adult poikilotherm is significantly more resistant as compared w ith that of the homeotherms. Similarly, the immature homeothermic heart is more resistant than the adult, possibly as a consequence of its greater cap ability for anaerobic glycolysis. Tolerance of the adult myocardium to oxyg en deprivation may be increased by pharmacological intervention, adaptation to chronic hypoxia, or preconditioning. Because the immature heart is sign ificantly more dependent on transsarcolemmal calcium entry to support contr action, the pharmacological protection achieved with drugs that interfere w ith calcium handling is markedly altered. Developing hearts demonstrated a greater sensitivity to calcium channel antagonists; a dose that induces onl y a small negative inotropic effect in adult rats stops the neonatal heart completely. Adaptation to chronic hypoxia results in similarly enhanced car diac resistance in animals exposed to hypoxia either immediately after birt h or in adulthood. Moreover, decreasing tolerance to ischemia during early postnatal life is counteracted by the development of endogenous protection; preconditioning failed to improve ischemic tolerance just after birth, but it developed during the early postnatal period. Basic knowledge of the pos sible improvements of immature heart tolerance to oxygen deprivation may co ntribute to the design of therapeutic strategies for both pediatric cardiol ogy and cardiac surgery.