title: Developmental determinants of cardiac sensitivity to hypoxia.
abstract: Cardiac sensitivity to oxygen deprivation changes significantly during ontogenetic development. However, the mechanisms for the higher tolerance of the immature heart, possibilities of protection, and the potential impact of perinatal hypoxia on cardiac tolerance to oxygen deprivation in adults have not yet been satisfactorily clarified. The hypoxic tolerance of an isolated rat heart showed a triphasic pattern: significant decrease from postnatal day 1 to 7, followed by increase to the weaning period, and final decline to adulthood. We have observed significant ontogenetic changes in mitochondrial oxidative phosphorylation and mitochondrial membrane potential, as well as in the role of the mitochondrial permeability transition pores in myocardial injury. These results support the hypothesis that cardiac mitochondria are deeply involved in the regulation of cardiac tolerance to oxygen deprivation during ontogenetic development. Ischemic preconditioning failed to increase tolerance to oxygen deprivation in the highly tolerant hearts of newborn rats. Chronic hypoxic exposure during early development may cause in-utero or neonatal programming of several genes that can change the susceptibility of the adult heart to ischemia-reperfusion injury; this effect is sex dependent. These results would have important clinical implications, since cardiac sensitivity in adult patients may be significantly affected by perinatal hypoxia in a sex-dependent manner.
authors.affiliation: a Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague, Czech Republic.
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Ostadal
authors.forename: Ivana
authors.initials: I
authors.lastname: Ostadalova
authors.forename: Frantisek
authors.initials: F
authors.lastname: Kolar
authors.forename: David
authors.initials: D
authors.lastname: Sedmera
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D005260:Female; D006321:Heart / Q000196:embryology* / Q000254:growth & development; D006801:Humans; D000860:Hypoxia / Q000196:embryology / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism; D017202:Myocardial Ischemia / Q000196:embryology / Q000209:etiology / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000378:metabolism*
keywords: cardiac protection; cœur immature; hypoxic tolerance; immature heart; ontogeny; ontogénie; protection cardiaque; tolérance hypoxique