Physiological Reviews, Vol. 79, No. 3, July 1999, pp. 635-659
Copyright ©1999 by the American Physiological Society
Development of Cardiac Sensitivity to Oxygen Deficiency:
Comparative and Ontogenetic Aspects
Bohuslav
Ostadal,
Ivana
Ostadalova, and
Naranjan S.
Dhalla
Institute of Physiology, Academy of Sciences of the Czech
Republic, Prague, Czech Republic; and Institute of Cardiovascular
Sciences, St. Boniface General Hospital Research Center, University of
Manitoba, Faculty of Medicine, Winnipeg,
Canada
Ostadal, Bohuslav,
Ivana Ostadalova, and
Naranjan S. Dhalla.
Development of Cardiac Sensitivity to Oxygen Deficiency:
Comparative and Ontogenetic Aspects. Physiol. Rev. 79: 635-659, 1999.
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 depends not only on the intensity
and duration of the hypoxic stimulus, but also on the level of cardiac
tolerance to oxygen deprivation. This variable changes significantly
during phylogenetic and ontogenetic development. The heart of an adult
poikilotherm is significantly more resistant as compared with that of
the homeotherms. Similarly, the immature homeothermic heart is more
resistant than the adult, possibly as a consequence of its greater
capability for anaerobic glycolysis. Tolerance of the adult myocardium
to oxygen deprivation may be increased by pharmacological intervention,
adaptation to chronic hypoxia, or preconditioning. Because the immature
heart is significantly more dependent on transsarcolemmal calcium entry
to support contraction, the pharmacological protection achieved with
drugs that interfere with calcium handling is markedly altered.
Developing hearts demonstrated a greater sensitivity to calcium channel
antagonists; a dose that induces only a small negative inotropic effect
in adult rats stops the neonatal heart completely. Adaptation to
chronic hypoxia results in similarly enhanced cardiac resistance in
animals exposed to hypoxia either immediately after birth 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 possible improvements of immature heart tolerance to
oxygen deprivation may contribute to the design of therapeutic
strategies for both pediatric cardiology and cardiac surgery.
