Epidemiological studies have demonstrated a relationship between the adverse influence of perinatal development and increased risk of ischemic heart disease in adults. From negative factors to which the fetus is subjected, the most important is hypoxia. The fetus may experience hypoxic stress under different conditions, including pregnancy at high altitude, pregnancy with anemia, placental insufficiency, and heart, lung, and kidney disease. One of the most common insults during the early stages of postnatal development is hypoxemia due to congenital cyanotic heart defects. Experimental studies have demonstrated a link between early hypoxia and increased risk of ischemia/reperfusion injury (I/R) in adults. Furthermore, it has been observed that late myocardial effects of chronic hypoxia, experienced in early life, may be sex-dependent. Unlike in males, perinatal hypoxia significantly increased cardiac tolerance to acute I/R injury in adult females, expressed as decreased infarct size and lower incidence of ischemic arrhythmias. It was suggested that early hypoxia may result in sex-dependent programming of specific genes in the offspring with the consequence of increased cardiac susceptibility to I/R injury in adult males. 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.
- MeSH
- dospělí MeSH
- hypoxie plodu komplikace patofyziologie MeSH
- ischemická choroba srdeční epidemiologie etiologie patofyziologie MeSH
- kyslík metabolismus MeSH
- lidé MeSH
- reperfuzní poškození myokardu epidemiologie etiologie patofyziologie MeSH
- rizikové faktory MeSH
- sexuální faktory MeSH
- srdce embryologie patofyziologie MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice epidemiologie etiologie patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Age and sex play an essential role in the cardiac tolerance to ischemia-reperfusion injury: cardiac resistance significantly decreases during postnatal maturation and the female heart is more tolerant than the male myocardium. It is widely accepted that mitochondrial dysfunction, and particularly mitochondrial permeability transition pore (MPTP) opening, plays a major role in determining the extent of cardiac ischemia-reperfusion injury. We have observed that the MPTP sensitivity to the calcium load differs in mitochondria isolated from neonatal and adult myocardium, as well as from adult male and female hearts. Neonatal and female mitochondria are more resistant both in the extent and in the rate of mitochondrial swelling induced by high calcium concentration. Our data further suggest that age- and sex-dependent specificity of the MPTP is not the result of different amounts of ATP synthase and cyclophilin D: neonatal and adult hearts, similarly as the male and female hearts, contain comparable amounts of MPTP and its regulatory protein cyclophilin D. We can speculate that the lower sensitivity of MPTP to the calcium-induced swelling may be related to the higher ischemic tolerance of both neonatal and female myocardium.
- MeSH
- lidé MeSH
- pohlavní dimorfismus * MeSH
- reperfuzní poškození myokardu metabolismus patologie patofyziologie MeSH
- srdce * patofyziologie MeSH
- srdeční mitochondrie metabolismus patologie MeSH
- transportní proteiny mitochondriální membrány metabolismus MeSH
- vápník metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Catecholamines are involved in the regulation of a wide variety of vital functions. The β-adrenergic receptor (β-AR) - adenylyl cyclase system has been identified early in embryogenesis before the heart has received adrenergic innervation. The structure of β-receptors in the immature myocardium is similar to that in adults; there are, however, significant quantitative developmental changes in the inotropic and chronotropic responsiveness. Information on the toxic effect of the β-AR agonists in the immature heart is surprisingly scarce, even though these agents are used in clinical practice both during pregnancy and in early postnatal development. Large doses of β-AR agonists induce malformations of the cardiovascular system; the type of change depends upon the time at which the β-AR agonist was administered during embryogenesis. During postnatal ontogeny, the cardiotoxicity of β-AR agonists increased from birth to adulthood. It seems likely that despite interspecies differences, developmental changes in the cardiac sensitivity to β-AR agonists may exist in all mammals, depending on the degree of maturation of the system involved in β-adrenergic signaling. All the existing data draw attention to the possible harmful consequences of the clinical use of β-AR agonists during early phases of cardiac development. Late effects of the early disturbances of the cardiac muscle cannot be excluded.
- MeSH
- adenylátcyklasy metabolismus MeSH
- agonisté adrenergních beta-receptorů škodlivé účinky MeSH
- beta-adrenergní receptory metabolismus MeSH
- kardiotoxicita etiologie MeSH
- katecholaminy škodlivé účinky MeSH
- lidé MeSH
- signální transdukce účinky léků MeSH
- srdce účinky léků embryologie MeSH
- těhotenství MeSH
- tokolytika škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Ischaemic heart disease (IHD) is the most frequent cause of mortality among men and women. Many epidemiological studies have demonstrated that premenopausal women have a reduced risk for IHD compared with their male counterparts. The incidence of IHD in women increases after menopause, suggesting that IHD is related to declining oestrogen levels. Experimental observations have confirmed the results of epidemiological studies investigating sex-specific differences in cardiac tolerance to ischaemia. Female sex appears also to favourably influence cardiac remodelling after ischaemia/reperfusion injury. Furthermore, sex-related differences in ischaemic tolerance of the adult myocardium can be influenced by interventions during the early phases of ontogenetic development. Detailed mechanisms of these sex-related differences remain unknown; however, they involve the genomic and non-genomic effects of sex steroid hormones, particularly the oestrogens, which have been the most extensively studied. Although the protective effects of oestrogen have many potential therapeutic implications, clinical trials have shown that oestrogen replacement in postmenopausal women may actually increase the incidence of IHD. The results of these trials have illustrated the complexity underlying the mechanisms involved in sex-related differences in cardiac tolerance to ischaemia. Sex-related differences in cardiac sensitivity to ischaemia/reperfusion injury may also influence therapeutic strategies in women with acute coronary syndrome. Women undergo coronary intervention less frequently and a lower proportion of women receive evidence-based therapy compared with men. Although our understanding of this important topic has increased in recent years, there is an urgent need for intensive experimental and clinical research to develop female-specific therapeutic strategies. Only then we will be able to offer patients better evidence-based treatment, a better quality of life and lower mortality.
- MeSH
- akutní koronární syndrom farmakoterapie metabolismus patofyziologie MeSH
- androgeny metabolismus MeSH
- estrogeny metabolismus MeSH
- ischemická choroba srdeční farmakoterapie metabolismus patofyziologie MeSH
- kardiovaskulární látky terapeutické užití MeSH
- lidé MeSH
- medicína založená na důkazech * MeSH
- myokard metabolismus MeSH
- náchylnost k nemoci MeSH
- pohlavní dimorfismus MeSH
- reperfuzní poškození myokardu prevence a kontrola MeSH
- srdce účinky léků patofyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- MeSH
- incidence MeSH
- kardiovaskulární fyziologické jevy * MeSH
- kardiovaskulární nemoci epidemiologie patofyziologie MeSH
- kardiovaskulární systém patofyziologie MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- rizikové faktory MeSH
- sexuální faktory * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- MeSH
- blokátory draslíkových kanálů MeSH
- draslíkové kanály chemie MeSH
- finanční podpora výzkumu jako téma MeSH
- fyziologická adaptace MeSH
- hypoxie MeSH
- oxid dusnatý metabolismus MeSH
- proteinkinasy chemie MeSH
- reaktivní formy kyslíku MeSH
- reperfuzní poškození myokardu genetika metabolismus MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- endoteliální růstové faktory analýza MeSH
- finanční podpora výzkumu jako téma MeSH
- krysa rodu rattus MeSH
- nechutenství genetika MeSH
- plíce fyziologie MeSH
- protoonkogenní proteiny c-fos fyziologie genetika MeSH
- protoonkogenní proteiny c-jun fyziologie genetika MeSH
- srdce fyziologie MeSH
- transformující růstový faktor beta analýza MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- MeSH
- adenylátcyklasy metabolismus MeSH
- finanční podpora výzkumu jako téma MeSH
- hypoxie enzymologie patologie MeSH
- isoprenalin farmakologie MeSH
- kolforsin farmakologie MeSH
- krysa rodu rattus MeSH
- myokard enzymologie MeSH
- nadmořská výška MeSH
- výšková nemoc enzymologie patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
