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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.

This review summarizes some available information on gender differences of myocardial injury with particular attention to experimental approach. It has been observed that significant gender differences exist already in normal heart. They involve among others cardiac growth, contractile function, calcium metabolism and function of mitochondria. Differences, characteristic of the normal myocardium, generate the logical presumption of the different reaction of the male and female heart to various pathogenic factors. Most of the experimental studies confirm the clinical observations: increased resistance of the female heart to ischemia/reperfusion injury was shown in dogs, rats, mice and rabbits. Furthermore, gender differences in the ischemic tolerance of the adult myocardium can be influenced by interventions (e.g. hypoxia) imposed during the early phases of ontogenetic development. The already high tolerance of the adult female heart can be increased by adaptation to chronic hypoxia and ischemic preconditioning. It seems that the protective effect depends on age: it was absent in young, highly tolerant heart but it appeared with the decrease of natural resistance during aging. Both experimental and clinical studies have indicated that female gender influences favorably also the remodeling and the adaptive response to myocardial infarction. It follows from the data available that male and female heart differs significantly in many parameters under both physiological and pathological conditions. Detailed molecular and cellular mechanisms of these differences are still unknown; they involve genomic and non-genomic effects of sex steroid hormones, particularly the most frequently studied estrogens. The cardiovascular system is, however, influenced not only by estrogens but also by other sex hormones, e.g. androgens. Moreover, steroid hormone receptors do not act alone but interact with a broad array of co-regulatory proteins to alter transcription. The differences are so important that they deserve serious consideration in clinical practice in search for proper diagnostic and therapeutic procedures.

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Reactive oxygen species (ROS) play several biological roles. We investigated the applicability of fluorescent probes for their detection (i) in rabbit lens epithelial cells during ageing in culture, and (ii) in thin sections of rat heart. We used dihydroethidium (DHE), dichlorofluorescin (DCFH), and dihydrorhodamine 123 (DHR) together with detection of autofluorescence both in cells and in chloroform extracts. Superoxide production was confirmed by a specific histochemical method using Mn(2+). All methods demonstrated higher production of ROS in older cells. All probes revealed different sites of ROS production in young and old cells and could be used for investigation of ROS generation during cell ageing. In the thin sections of rat heart DCFH was not suitable for intracellular ROS detection. The results indicate that the potential of fluorescent dyes in ROS detection is not usually fully exploited, and that blue autofluorescence is associated with oxidative damage.

Rat hearts isolated on d 1, 4, 7, and 10 of postnatal life were perfused (in Langendorff mode) with Krebs-Henseleit solution at constant pressure, temperature, and stimulation rate. Recovery of the contractile function after global ischemia was measured by an isometric force transducer and analyzed using an online computer. Ischemic preconditioning (IP) was induced by three 3-min periods of global ischemia, each separated by a 5-min period of reperfusion. Prenatal hypoxia was induced by exposure of pregnant mothers to intermittent high altitude (IHA), simulated in a barochamber (8 h/d, 5000 m) from d 15 to 20 of pregnancy. Postnatal hypoxia was simulated by the identical procedure from postnatal d 1 to 6 and 9. Prenatal exposure to IHA failed to improve ischemic tolerance on d 1, but postnatal exposure to IHA improved recovery of the developed force after ischemia on d 7 (33 +/- 3% versus 43 +/- 4%) and 10 (39 +/- 2% versus 54 +/- 2%). Combination of IHA and IP induced higher protective effects in all age groups, including postnatal d 1 (48 +/- 2% versus 56 +/- 3%), whereas IHA and IP applied separately failed to improve ischemic tolerance. Neither the mitochondrial K(ATP) channel blocker 5-hydroxydecanoate nor the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester abolished protection by IP in normoxic animals, but they decreased significantly protection by IHA hypoxia. The final recovery was even lower than the corresponding normoxic values. It seems likely that mitochondrial K(ATP) channels and nitric oxide may be involved in the protective mechanisms of adaptation to chronic hypoxia but not to that of IP, at least in neonates.