Experimental and clinical studies have clearly demonstrated significant sex differences in myocardial structure and function, both under physiological and pathological conditions. The best example are significant sex differences in the cardiac tolerance to ischemia/reperfusion injury: pre-menopausal adult female hearts are more resistant as compared to the male myocardium. The importance of these findings is supported by the fact that the number of studies dealing with this issue increased significantly in recent years. Detailed molecular and cellular mechanisms responsible for sex differences are yet to be elucidated; however, it has been stressed that the differences cannot be explained only by the effect of estrogens. In recent years, a promising new hypothesis has been developed, suggesting that mitochondria may play a significant role in the sex differences in cardiac tolerance to oxygen deprivation. However, one is clear already today: sex differences are so important that they should be taken into consideration in the clinical practice for the selection of the optimal diagnostic and therapeutic strategy in the treatment of ischemic heart disease. The present review attempts to summarize the progress in cardiovascular research on sex-related differences in cardiac tolerance to oxygen deprivation during the last 40 years, i.e. from the first experimental observation. Particular attention was paid to the sex-related differences of the normal heart, sex-dependent tolerance to ischemia-reperfusion injury, the role of hormones and, finally, to the possible role of cardiac mitochondria in the mechanism of sex-dependent differences in cardiac tolerance to ischemia/reperfusion injury. Key words: Female heart, Cardiac hypoxic tolerance, Ischemia-reperfusion injury, Sex differences.

• MeSH
• kyslík metabolismus   MeSH
• lidé MeSH
• myokard metabolismus   patologie   MeSH
• pohlavní dimorfismus * MeSH
• reperfuzní poškození myokardu metabolismus   patofyziologie   MeSH
• sexuální faktory MeSH
• srdeční mitochondrie metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• kyslík MeSH

The cardioprotective effect of ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) in adult hearts is mediated by nitric oxide (NO). During the early developmental period, rat hearts exhibit higher resistance to ischemia-reperfusion (I/R) injury, contain higher levels of serum nitrates, and their resistance cannot be further increased by IPC or IPoC. NOS blocker (L-NAME) lowers their high resistance. Wistar rat hearts (postnatal Days 1 and 10) were perfused according to Langendorff and exposed to 40 min of global ischemia followed by reperfusion with or without IPoC. NO and reactive oxygen species donors (DEA-NONO, SIN-1) and L-NAME were administered. Tolerance to ischemia decreased between Days 1 and 10. DEA-NONO (low concentrations) significantly increased tolerance to I/R injury on both Days 1 and 10. SIN-1 increased tolerance to I/R injury on Day 10, but not on Day 1. L-NAME significantly reduced resistance to I/R injury on Day 1, but actually increased resistance to I/R injury on Day 10. Cardioprotection by IPoC on Day 10 was not affected by either NO donors or L-NAME. It can be concluded that resistance of the neonatal heart to I/R injury is NO dependent, but unlike in adult hearts, cardioprotective interventions, such as IPoC, are most likely NO independent.

• Klíčová slova
• DEA‐NONO, L‐NAME, SIN‐1, ischemic postconditioning, neonatal hearts, nitric oxide,
• MeSH
• donory oxidu dusnatého farmakologie   MeSH
• ischemické přivykání metody   MeSH
• ischemický postconditioning * metody   MeSH
• krysa rodu Rattus MeSH
• molsidomin farmakologie   analogy a deriváty   MeSH
• myokard metabolismus   MeSH
• NG-nitroargininmethylester * farmakologie   MeSH
• novorozená zvířata * MeSH
• oxid dusnatý * metabolismus   MeSH
• potkani Wistar * MeSH
• reperfuzní poškození myokardu * prevence a kontrola   metabolismus   MeSH
• srdce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• donory oxidu dusnatého MeSH
• molsidomin MeSH
• NG-nitroargininmethylester * MeSH
• oxid dusnatý * MeSH

In 2023, six decades have elapsed since the first experimental work on the heart muscle was published, in which a member of the Institute of Physiology of the Czech Academy of Sciences participated as an author; Professor Otakar Poupa was the founder and protagonist of this research domain. Sixty years - more than half of the century - is certainly significant enough anniversary that is worth looking back and reflecting on what was achieved during sometimes very complicated periods of life. It represents the history of an entire generation of experimental cardiologists; it is possible to learn from its successes and mistakes. The objective of this review is to succinctly illuminate the scientific trajectory of an experimental cardiological department over a 60-year span, from its inaugural publication to the present. The old truth - historia magistra vitae - is still valid. Keywords: Heart, Adaptation, Development, Hypoxia, Protection.

• MeSH
• akademie a ústavy * dějiny   MeSH
• biomedicínský výzkum * dějiny   trendy   MeSH
• dějiny 20. století MeSH
• dějiny 21. století MeSH
• fyziologie dějiny   MeSH
• kardiologie dějiny   trendy   MeSH
• lidé MeSH
• srdce fyziologie   MeSH
• zvířata MeSH
• Check Tag
• dějiny 20. století MeSH
• dějiny 21. století MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• historické články MeSH
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH

Cardioprotective effect of ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) in adult hearts is mediated by mitochondrial-K-ATP channels and nitric oxide (NO). During early developmental period, rat hearts exhibit higher resistance to ischemia-reperfusion (I/R) injury and their resistance cannot be further increased by IPC or IPoC. Therefore, we have speculated, whether mechanisms responsible for high resistance of neonatal heart may be similar to those of IPC and IPoC. To test this hypothesis, rat hearts isolated on days 1, 4, 7, and 10 of postnatal life were perfused according to Langendorff. Developed force (DF) of contraction was measured. Hearts were exposed to 40 min of global ischemia followed by reperfusion up to the maximum recovery of DF. IPoC was induced by 5 cycles of 10-s ischemia. Mito-K-ATP blocker (5-HD) was administered 5 min before ischemia and during first 20 min of reperfusion. Another group of hearts was isolated for biochemical analysis of 3-nitrotyrosine, and serum samples were taken to measure nitrate levels. Tolerance to ischemia did not change from day 1 to day 4 but decreased on days 7 and 10. 5-HD had no effect either on neonatal resistance to I/R injury or on cardioprotective effect of IPoC on day 10. Significant difference was found in serum nitrate levels between days 1 and 10 but not in tissue 3-nitrotyrosine content. It can be concluded that while there appears to be significant difference of NO production, mito-K-ATP and ROS probably do not play role in the high neonatal resistance to I/R injury.

• Klíčová slova
• 3-Nitrotyrosine, Ischemic postconditioning, Mito-K-ATP channel, Neonatal rats, Nitrates, Tolerance to ischemia,
• MeSH
• draslíkové kanály metabolismus   MeSH
• ischemický postconditioning * MeSH
• krysa rodu Rattus MeSH
• novorozená zvířata MeSH
• oxid dusnatý metabolismus   MeSH
• potkani Wistar MeSH
• reperfuzní poškození myokardu metabolismus   patofyziologie   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• draslíkové kanály MeSH
• mitochondrial K(ATP) channel MeSH Prohlížeč
• oxid dusnatý 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.

• Klíčová slova
• acute coronary syndrome, cardioprotection, heart, ischaemia/reperfusion injury, oestrogen, sex differences, therapeutic implications,
• 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
• Názvy látek
• androgeny MeSH
• estrogeny MeSH
• kardiovaskulární látky MeSH

Postnatal maturation of the heart is characterized by decreasing tolerance to ischemia/reperfusion (I/R) injury associated with significant changes in mitochondrial function. The aim of this study is to test the hypothesis that the role of the mitochondrial membrane permeability transition pore (MPTP) in the I/R injury differs in the neonatal and in the adult heart. For this purpose, the effect of blockade of MPTP on the degree of I/R injury and the sensitivity of MPTP to swelling-inducing agents was compared in hearts from neonatal (7 days old) and adult (90 days old) Wistar rats. It was found that the release of NAD(+) from the perfused heart induced by I/R can be prevented by sanglifehrin A (SfA) only in the adult myocardium; SfA had no protective effect in the neonatal heart. Furthermore, the extent of Ca-induced swelling of mitochondria from neonatal rats was significantly lower than that from the adult animals; mitochondria from neonatal rats were more resistant at higher concentrations of calcium. In addition, not only the extent but also the rate of calcium-induced swelling was about twice higher in adult than in neonatal mitochondria. The results support the idea that lower sensitivity of the neonatal MPTP to opening may be involved in the mechanism of the higher tolerance of the neonatal heart to I/R injury.

• MeSH
• krysa rodu Rattus MeSH
• laktony farmakologie   MeSH
• novorozená zvířata MeSH
• potkani Wistar MeSH
• přechodový pór mitochondriální permeability MeSH
• reperfuzní poškození metabolismus   MeSH
• spirosloučeniny farmakologie   MeSH
• srdeční mitochondrie metabolismus   MeSH
• transportní proteiny mitochondriální membrány metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• laktony MeSH
• přechodový pór mitochondriální permeability MeSH
• sanglifehrin A MeSH Prohlížeč
• spirosloučeniny MeSH
• transportní proteiny mitochondriální membrány MeSH

The aim of the study was to find out whether administration of selenium (Se) will protect the immature heart against ischemia/reperfusion.The control pregnant rats were fed laboratory diet (0.237 mg Se/kg diet); experimental rats received 2 ppm Na(2)SeO(3) in the drinking water from the first day of pregnancy until day 10 post partum. The concentration of Se in the serum and heart tissue was determined by activation analysis, the serum concentration of NO by chemiluminescence, cardiac concentration of lipofuscin-like pigment by fluorescence analysis. The 10 day-old hearts were perfused (Langendorff); recovery of developed force (DF) was measured after 40 min of global ischemia. In acute experiments, 10 day-old hearts were perfused with selenium (75 nmol/l) before or after global ischemia. Sensitivity to isoproterenol (ISO, pD(50)) was assessed as a response of DF to increasing cumulative dose.Se supplementation elevated serum concentration of Se by 16%. Se increased ischemic tolerance (recovery of DF, 32.28 +/- 2.37 vs. 41.82 +/- 2.91%, P < 0.05). Similar results were obtained after acute administration of Se during post-ischemic reperfusion (32.28 +/- 2.37 vs. 49.73 +/- 4.40%, P < 0.01). The pre-ischemic treatment, however, attenuated the recovery (23.08 +/- 3.04 vs. 32.28 +/- 2.37%, P < 0.05). Moreover, Se supplementation increased the sensitivity to the inotropic effect of ISO, decreased cardiac concentration of lipofuscin-like pigment and serum concentration of NO. Our results suggest that Se protects the immature heart against ischemia/reperfusion injury. It seems therefore, that ROS may affect the function of the neonatal heart, similarly as in adults.

• MeSH
• časové faktory MeSH
• ischemická choroba srdeční farmakoterapie   prevence a kontrola   MeSH
• kontrakce myokardu účinky léků   MeSH
• krysa rodu Rattus MeSH
• lipofuscin metabolismus   MeSH
• oxid dusnatý krev   MeSH
• perfuze MeSH
• potkani Wistar MeSH
• potravní doplňky MeSH
• reperfuzní poškození myokardu farmakoterapie   prevence a kontrola   MeSH
• selen krev   farmakologie   terapeutické užití   MeSH
• srdce účinky léků   MeSH
• těhotenství MeSH
• tělesná hmotnost účinky léků   MeSH
• velikost orgánu účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• lipofuscin MeSH
• oxid dusnatý MeSH
• selen MeSH