Delayed reperfusion of the ischemic heart (I/R) is known to impair the recovery of cardiac function and produce a wide variety of myocardial defects, including ultrastructural damage, metabolic alterations, subcellular Ca2+-handling abnormalities, activation of proteases, and changes in cardiac gene expression. Although I/R injury has been reported to induce the formation of reactive oxygen species (ROS), inflammation, and intracellular Ca2+ overload, the generation of oxidative stress is considered to play a critical role in the development of cardiac dysfunction. Increases in the production of superoxide, hydroxyl radicals, and oxidants, such as hydrogen peroxide and hypochlorous acid, occur in hearts subjected to I/R injury. In fact, mitochondria are a major source of the excessive production of ROS in I/R hearts due to impairment in the electron transport system as well as activation of xanthine oxidase and NADPH oxidase. Nitric oxide synthase, mainly present in the endothelium, is also activated due to I/R injury, leading to the production of nitric oxide, which, upon combination with superoxide radicals, generates nitrosative stress. Alterations in cardiac function, sarcolemma, sarcoplasmic reticulum Ca2+-handling activities, mitochondrial oxidative phosphorylation, and protease activation due to I/R injury are simulated upon exposing the heart to the oxyradical-generating system (xanthine plus xanthine oxidase) or H2O2. On the other hand, the activation of endogenous antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, and the concentration of a transcription factor (Nrf2), which modulates the expression of various endogenous antioxidants, is depressed due to I/R injury in hearts. Furthermore, pretreatment of hearts with antioxidants such as catalase plus superoxide dismutase, N-acetylcysteine, and mercaptopropionylglycerine has been observed to attenuate I/R-induced subcellular Ca2+ handling and changes in Ca2+-regulatory activities; additionally, it has been found to depress protease activation and improve the recovery of cardiac function. These observations indicate that oxidative stress is intimately involved in the pathological effects of I/R injury and different antioxidants attenuate I/R-induced subcellular alterations and improve the recovery of cardiac function. Thus, we are faced with the task of developing safe and effective antioxidants as well as agents for upregulating the expression of endogenous antioxidants for the therapy of I/R injury.

• Keywords
• Ca2+-handling abnormalities, antioxidants, cardiac dysfunction, ischemia–reperfusion injury, oxidative stress, subcellular defects,
• Publication type
• Journal Article MeSH
• Review MeSH

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
• Oxygen metabolism   MeSH
• Humans MeSH
• Myocardium metabolism   pathology   MeSH
• Sex Characteristics * MeSH
• Myocardial Reperfusion Injury metabolism   physiopathology   MeSH
• Sex Factors MeSH
• Mitochondria, Heart metabolism   pathology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Oxygen 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.

• Keywords
• DEA‐NONO, L‐NAME, SIN‐1, ischemic postconditioning, neonatal hearts, nitric oxide,
• MeSH
• Nitric Oxide Donors pharmacology   MeSH
• Ischemic Preconditioning, Myocardial methods   MeSH
• Ischemic Postconditioning * methods   MeSH
• Rats MeSH
• Molsidomine pharmacology   analogs & derivatives   MeSH
• Myocardium metabolism   MeSH
• NG-Nitroarginine Methyl Ester * pharmacology   MeSH
• Animals, Newborn * MeSH
• Nitric Oxide * metabolism   MeSH
• Rats, Wistar * MeSH
• Myocardial Reperfusion Injury * prevention & control   metabolism   MeSH
• Heart drug effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Nitric Oxide Donors MeSH
• Molsidomine MeSH
• NG-Nitroarginine Methyl Ester * MeSH
• Nitric Oxide * 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
• Academies and Institutes * history   MeSH
• Biomedical Research * history   trends   MeSH
• History, 20th Century MeSH
• History, 21st Century MeSH
• Physiology history   MeSH
• Cardiology history   trends   MeSH
• Humans MeSH
• Heart physiology   MeSH
• Animals MeSH
• Check Tag
• History, 20th Century MeSH
• History, 21st Century MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Historical Article MeSH
• Review MeSH
• Geographicals
• Czech Republic MeSH

The mitochondrial permeability transition pore (MPTP) is a calcium-dependent, ion non-selective membrane pore with a wide range of functions. Although the MPTP has been studied for more than 50 years, its molecular structure remains unclear. Short-term (reversible) opening of the MPTP protects cells from oxidative damage and enables the efflux of Ca2+ ions from the mitochondrial matrix and cell signaling. However, long-term (irreversible) opening induces processes leading to cell death. Ca2+ ions, reactive oxygen species, and changes in mitochondrial membrane potential regulate pore opening. The sensitivity of the pore to Ca2+ ions changes as an organism ages, and MPTP opening plays a key role in the pathogenesis of many diseases. Most studies of the MPTP have focused on elucidating its molecular structure. However, understanding the mechanisms that will inhibit the MPTP may improve the treatment of diseases associated with its opening. To evaluate the functional state of the MPTP and its inhibitors, it is therefore necessary to use appropriate methods that provide reproducible results across laboratories. This review summarizes our current knowledge of the function and regulation of the MPTP. The latter part of the review introduces two optimized methods for evaluating the functional state of the pore under standardized conditions.

• Keywords
• calcium retention capacity, calcium signaling, calcium-induced swelling, mitochondria, mitochondrial permeability transition, mitochondrial permeability transition pore,
• MeSH
• Cell Death MeSH
• Mitochondria metabolism   MeSH
• Mitochondrial Permeability Transition Pore * metabolism   MeSH
• Mitochondrial Membrane Transport Proteins * metabolism   MeSH
• Calcium metabolism   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Mitochondrial Permeability Transition Pore * MeSH
• Mitochondrial Membrane Transport Proteins * MeSH
• Calcium MeSH

Methylphenidate is commonly used for the treatment of attention deficit hyperactivity disorder. The cardiovascular safety of methylphenidate has been a subject of debate with some studies indicating that methylphenidate increases the likelihood of experiencing a myocardial infarction. However, it is unknown whether methylphenidate worsens the extent of injury during an ischemic insult. The purpose of this study was to determine whether short term exposure to methylphenidate increases the extent of myocardial injury during an ischemic insult. Male and female rats received methylphenidate (5 mg/kg/day) or saline for 10 days by oral gavage. Hearts were subjected to 20 min of ischemia and 2 h of reperfusion on a Langendorff isolated heart apparatus on day 11. Cardiac contractile function was monitored via an intraventricular balloon and myocardial injury was assessed by triphenyltetrazolium chloride staining. Methylphenidate significantly increased locomotor activity in male and female rats, confirming absorption of this psychostimulant into the central nervous system. Male hearts had significantly larger infarcts than female hearts, but methylphenidate had no impact on infarct size or postischemic recovery of contractile function in hearts of either sex. These data indicate that methylphenidate does not increase the extent of injury induced by an ischemic insult.

• MeSH
• Myocardial Infarction chemically induced   pathology   MeSH
• Myocardial Ischemia chemically induced   pathology   MeSH
• Myocardial Contraction drug effects   MeSH
• Rats MeSH
• Methylphenidate adverse effects   pharmacology   MeSH
• Disease Models, Animal MeSH
• Recovery of Function MeSH
• Rats, Sprague-Dawley MeSH
• Drug Administration Schedule MeSH
• Central Nervous System Stimulants pharmacology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Methylphenidate MeSH
• Central Nervous System Stimulants MeSH

Values of the calcium retention capacity (CRC) of rat liver mitochondria are highly dependent on the experimental conditions used. When increasing amounts of added calcium chloride are used (1.25-10 nmol), the values of the CRC increase 3-fold. When calcium is added in 75 s intervals, the CRC values increase by 30 % compared with 150 s interval additions. CRC values are not dependent on the calcium/protein ratio in the measured sample in our experimental design. We also show that a more detailed evaluation of the fluorescence curves can provide new information about mitochondrial permeability transition pore opening after calcium is added.

• MeSH
• Biological Transport MeSH
• Mitochondria, Liver metabolism   MeSH
• Liver metabolism   MeSH
• Rats MeSH
• Mitochondrial Membranes metabolism   MeSH
• Permeability MeSH
• Mitochondrial Permeability Transition Pore metabolism   MeSH
• Mitochondrial Membrane Transport Proteins metabolism   MeSH
• Calcium metabolism   MeSH
• Research Design MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Evaluation Study MeSH
• Names of Substances
• Mitochondrial Permeability Transition Pore MeSH
• Mitochondrial Membrane Transport Proteins MeSH
• Calcium 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.

• Keywords
• 3-Nitrotyrosine, Ischemic postconditioning, Mito-K-ATP channel, Neonatal rats, Nitrates, Tolerance to ischemia,
• MeSH
• Potassium Channels metabolism   MeSH
• Ischemic Postconditioning * MeSH
• Rats MeSH
• Animals, Newborn MeSH
• Nitric Oxide metabolism   MeSH
• Rats, Wistar MeSH
• Myocardial Reperfusion Injury metabolism   physiopathology   prevention & control   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Potassium Channels MeSH
• mitochondrial K(ATP) channel MeSH Browser
• Nitric Oxide MeSH