Impact of Perinatal Chronic Hypoxia on Cardiac Tolerance to Acute Ischemia

  • Bohuslav Ostadal
  • I. Ostadalova
  • F. Kolar
  • I. Netuka
  • O. Szarszoi


Perinatal period is critical for the normal cardiac development, and different interventions imposed on the heart may significantly influence myocardial structure and function. Perinatal hypoxemia, although transient, may thus have serious early and late consequences on the cardiovascular system. Epidemiological and experimental studies have repeatedly suggested a possible link between perinatal hypoxia and increased sensitivity to ischemia/reperfusion (I/R) injury in adults. The mechanisms of this increased susceptibility are not known at present. It has been found that prenatal chronic hypoxia sensitizes the apoptosis pathway in the adult male heart in response to I/R stimulation. In addition, cardiac heat shock proteins (Hsp) 70 expression was significantly lower in prenatal hypoxic hearts than in controls; this fact may play a role in the increased susceptibility of the adult heart to I/R injury. The decreased eNOS levels in adult prenatal hypoxic hearts may also contribute to their increased sensitivity. These studies suggest that chronic hypoxic exposure during early development may cause in utero or neonatal programming of several genes which can play an important role in the increased susceptibility of the adult male heart to I/R injury. Furthermore, it has been observed in the rat model that late myocardial effects of chronic hypoxia, experienced in early life, may be sex-dependent. Unlike in males, perinatal exposure to chronic hypoxia significantly increased cardiac tolerance to acute I/R injury in adult females, expressed as the lower incidence of ischemic arrhythmias, decreased infarct size, decreased cardiac enzyme release, and increased postischemic recovery of left ventricular function. It was suggested that these sex-dependent changes may be due to differences in fetal programming of PKCε gene expression, which play a pivotal role in cardioprotection; down-regulation of PKCε function was observed in the hearts of adult male offspring only. These results would have important clinical implications, since cardiac sensitivity to oxygen deprivation in adult patients may be significantly influenced by perinatal hypoxia in a sex-dependent manner.


Perinatal period Fetal heart Neonatal heart Cardiac development Mitochondrial development Chronic hypoxia Cardiac tolerance to ischemia Infarct size Arrhythmias Barker’s concept Ischemia/reperfusion injury Prenatal hypoxia Early postnatal hypoxia Late effects of perinatal hypoxia Sex-dependent changes 



This study was supported by grants MSMT 1 M0510 and AVOZ 50110509.


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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Bohuslav Ostadal
    • 1
    • 2
  • I. Ostadalova
    • 3
    • 2
  • F. Kolar
    • 3
    • 2
  • I. Netuka
    • 1
    • 4
  • O. Szarszoi
    • 5
  1. 1.Centre for Cardiovascular ResearchPragueCzech Republic
  2. 2.Institute of Physiology, Academy of Sciences of the Czech RepublicPragueCzech Republic
  3. 3.Centre for Cardiovascular Research, Academy of Sciences of the Czech RepublicPragueCzech Republic
  4. 4.Institute for Clinical and Experimental MedicinePragueCzech Republic
  5. 5.Centre for Cardiovascular Research, Institute for Clinical and Experimental MedicinePragueCzech Republic

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