BackgroundThe ischemia-reperfusion injury (IRI) is unavoidable in vascular surgery. Damage to the microcirculation and endothelial glycocalyx might set up a shock with loss of circulatory coherence and organ failure. Sulodexide may help to protect endothelial glycocalyx and alleviate the ischemia-reperfusion injury.MethodsTwenty female piglets underwent surgery with a 30-min-long suprarenal aortic clamp, followed by two hours of reperfusion. Ten piglets received sulodexide before the clamp, and 10 received normal saline. Blood and urine samples were taken at baseline and in 20-min intervals until the 120th minute to analyze the serum syndecan-1, E-selectin, and thrombomodulin. Albumin and glycosaminoglycans were examined in the urine. The kidney biopsies before and after the protocol were examined by light microscopy with hematoxylin-eosin staining. The sublingual microcirculation was recorded by side-stream dark field imaging at the time as blood and urine.ResultsBased on the 2-way ANOVA testing, there was no statistically significant difference in the parameters of sublingual microcirculation. Serum markers of endothelial cell activation and damage (E-selectin and thrombomodulin) did not show any statistically significant difference either. Syndecan-1, a marker of glycocalyx damage, showed statistically significantly higher values based on the 2-way ANOVA testing (p < 0.0001) with the highest difference in the 80th minute: 7.8 (3.9-44) ng/mL in the control group and 1.8 (0.67-2.8) ng/mL in the sulodexide group. In the urine, the albuminuria was higher in the control group, although not statistically significant. Glycosaminoglycans were statistically significantly higher in the sulodexide group based on the mixed-effect analysis due to the intervention itself. Histological analysis of the renal biopsies showed necrosis in both groups after reperfusion.ConclusionAdministering sulodexide significantly reduced the level of endothelial markers of IRI. The study results support further research into using preemptive administration of sulodexide to modulate IRI in clinical medicine.

• MeSH
• E-Selectin blood   MeSH
• Glycocalyx MeSH
• Glycosaminoglycans * pharmacology   therapeutic use   MeSH
• Kidney pathology   blood supply   MeSH
• Microcirculation drug effects   MeSH
• Disease Models, Animal MeSH
• Swine MeSH
• Reperfusion Injury * prevention & control   MeSH
• Syndecan-1 blood   MeSH
• Thrombomodulin blood   MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Animal models are an important tool for studying ischemic mechanisms of stroke. Among them, the middle cerebral artery occlusion (MCAO) model via the intraluminal suture method in rodents is closest to human ischemic stroke. It is a model of transient occlusion followed by reperfusion, thus representing cerebral ischemia-reperfusion model that simulates patients with vascular occlusion and timely recanalization. Although reperfusion is very beneficial for the possibility of preserving brain functions after ischemia, it also brings a great risk in the form of brain edema, which can cause the development of intracranial hypertension, and increasing morbidity and mortality. In this paper, we present the results of our own transient reperfusion model of MCAO in which we tested the permeability of the blood-brain barrier (BBB) using Evans blue (EB), an intravital dye with a high molecular weight (68,500 Da) that prevents its penetration through the intact BBB. A total of 15 animals were used in the experiment and underwent the following procedures: insertion of the MCA occluder; assessment of ischemia by 2,3,5 -Triphenyltetrazolium chloride (TTC) staining; assessment of the BBB permeability using brain EB distribution. The results are presented and discussed. The test of BBB permeability using EB showed that 120 minutes after induction of ischemia, the BBB is open for the entry of large molecules into the brain. We intend to use this finding to time the application of neuroprotective agents via ICA injection in our next stroke model. Keywords: Cerebral ischemia-reperfusion model, Middle cerebral artery occlusion, Blood-brain barrier, 2,3,5 -Triphenyltetrazolium chloride, Evans blue.

• MeSH
• Evans Blue MeSH
• Blood-Brain Barrier * metabolism   MeSH
• Infarction, Middle Cerebral Artery * metabolism   MeSH
• Brain Ischemia metabolism   MeSH
• Capillary Permeability MeSH
• Rats MeSH
• Disease Models, Animal * MeSH
• Permeability MeSH
• Pilot Projects MeSH
• Rats, Sprague-Dawley MeSH
• Reperfusion Injury * metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Metabolic syndrome (MetS) represents a worldwide health problem, affecting cardiovascular and mental health. People with MetS are often suffering from depression. We used hereditary hypertriacylglycerolemic (HTG) rats as an animal model of MetS, and these were fed a high-fat-high-fructose diet (HFFD) to imitate unhealthy eating habits of people having several MetS risk factors and suffering depression. Male HTG rats were fed a standard diet (HTG-SD) or HFFD for eight weeks (HFFD8). Venlafaxine was administered for the last three weeks of the experiment (HFFD8+VE). Heart function was observed on the level of intact organisms (standard ECG in vivo), isolated hearts (perfusion according to Langendorff ex vivo), and molecular level, using the RT-PCR technique. The function of the isolated perfused heart was monitored under baseline and ischemia/reperfusion conditions. Analysis of ECG showed electrical abnormalities in vivo, such as significant QRS complex prolongation and increased heart rate. Ex vivo venlafaxine significantly reduced QT interval after ischemia/reperfusion injury. Baseline values of contractile abilities of the heart tended to be suppressed by HFFD. A significant reduction of LVDP was present in the HFFD8 group. Molecular analysis of specific genes involved in cardiac electrical (Cacna1c, Scn5a), contractile (Myh6, Myh7), metabolic function (Pgc1alpha) and calcium handling (Serca2a, Ryr2) supported some of the functional findings in vivo and ex vivo. Based on the present effect of venlafaxine on heart function, further research is needed regarding its cardiometabolic safety in the treatment of patients with MetS suffering from depression. Keywords: Metabolic syndrome, Venlafaxine, ECG, Cardiac contraction, Ischemia/Reperfusion.

• MeSH
• Diet, High-Fat * adverse effects   MeSH
• Fructose * administration & dosage   MeSH
• Cardiovascular Diseases MeSH
• Rats MeSH
• Metabolic Syndrome genetics   MeSH
• Disease Models, Animal MeSH
• Heart Disease Risk Factors MeSH
• Venlafaxine Hydrochloride * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

An excessive increase in reactive oxygen species (ROS) levels is one of the main causes of mitochondrial dysfunction. However, when ROS levels are maintained in balance with antioxidant mechanisms, ROS fulfill the role of signaling molecules and modulate various physiological processes. Recent advances in mitochondrial bioenergetics research have revealed a significant interplay between mitochondrial peroxiredoxins (PRDXs) and monoamine oxidase-A (MAO-A) in regulating ROS levels. Both proteins are associated with hydrogen peroxide (H2O2), MAO-A as a producer and PRDXs as the primary antioxidant scavengers of H2O2. This review focuses on the currently available knowledge on the function of these proteins and their interaction, highlighting their importance in regulating oxidative damage, apoptosis, and metabolic adaptation in the heart. PRDXs not only scavenge excess H2O2, but also act as regulatory proteins, play an active role in redox signaling, and maintain mitochondrial membrane integrity. Overexpression of MAO-A is associated with increased oxidative damage, leading to mitochondrial dysfunction and subsequent progression of cardiovascular diseases (CVD), including ischemia/reperfusion injury and heart failure. Considering the central role of oxidative damage in the pathogenesis of many CVD, targeting PRDXs activation and MAO-A inhibition may offer new therapeutic strategies aimed at improving cardiac function under conditions of pathological load related to oxidative damage. Keywords: Mitochondria, Peroxiredoxin, Monoamine oxidase-A, Reactive oxygen species, Cardioprotective signaling.

• MeSH
• Humans MeSH
• Monoamine Oxidase * metabolism   MeSH
• Oxidative Stress MeSH
• Peroxiredoxins * metabolism   MeSH
• Reactive Oxygen Species * metabolism   MeSH
• Signal Transduction * MeSH
• Mitochondria, Heart metabolism   enzymology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Extracellular potassium concentration might modify electrophysiological properties in the border zone of ischemic myocardium. We evaluated the depolarization and repolarization characteristics across the ischemic-normal border under [K+] variation. Sixty-four-lead epicardial mapping was performed in 26 rats ([K+] 2.3-6.4 mM) in a model of acute ischemia/reperfusion. The animals with [K+] < 4.7 mM (low-normal potassium) had an ischemic zone with ST-segment elevation and activation delay, a border zone with ST-segment elevation and no activation delay, and a normal zone without electrophysiological abnormalities. The animals with [K+] >4.7 mM (normal-high potassium) had only the ischemic and normal zones and no transitional area. Activation-repolarization intervals and local conduction velocities were inversely associated with [K+] in linear regression analysis with adjustment for the zone of myocardium. The reperfusion extrasystolic burden (ESB) was greater in the low-normal as compared to normal-high potassium animals. Ventricular tachycardia/fibrillation incidence did not differ between the groups. In patch-clamp experiments, hypoxia shortened action potential duration at 5.4 mM but not at 1.3 mM of [K+]. IK(ATP) current was lower at 1.3 mM than at 5.4 mM of [K+]. We conclude that the border zone formation in low-normal [K+] was associated with attenuation of IK(ATP) response to hypoxia and increased reperfusion ESB.

• MeSH
• Action Potentials * physiology   MeSH
• Potassium * blood   metabolism   MeSH
• Myocardial Ischemia * physiopathology   blood   metabolism   MeSH
• Rats MeSH
• Rats, Wistar MeSH
• Myocardial Reperfusion Injury blood   physiopathology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article 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

The aim of the study was to examine the potential role of mitochondrial permeability transition pore (mPTP) in the cardioprotective effect of chronic continuous hypoxia (CH) against acute myocardial ischemia/reperfusion (I/R) injury. Adult male Wistar rats were adapted to CH for 3 weeks, while their controls were kept under normoxic conditions. Subsequently, they were subjected to I/R insult while being administered with mPTP inhibitor, cyclosporin A (CsA). Infarct size and incidence of ischemic and reperfusion arrhythmias were determined. Our results showed that adaptation to CH as well as CsA administration reduced myocardial infarct size in comparison to the corresponding control groups. However, administration of CsA did not amplify the beneficial effect of CH, suggesting that inhibition of mPTP opening contributes to the protective character of CH.

• MeSH
• Chronic Disease MeSH
• Cyclosporine * pharmacology   MeSH
• Hypoxia * metabolism   MeSH
• Myocardial Infarction metabolism   pathology   prevention & control   MeSH
• Rats MeSH
• Rats, Wistar * MeSH
• Mitochondrial Permeability Transition Pore * metabolism   MeSH
• Myocardial Reperfusion Injury * metabolism   prevention & control   pathology   MeSH
• Mitochondria, Heart metabolism   drug effects   pathology   MeSH
• Mitochondrial Membrane Transport Proteins metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article 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.

• 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

• MeSH
• Biochemistry MeSH
• Metabolic Diseases MeSH
• Pathology MeSH

• Conspectus
• Patologie. Klinická medicína
• Učební osnovy. Vyučovací předměty. Učebnice
• NML Fields
• biochemie
• patologie
• NML Publication type
• učebnice vysokých škol

Ischemická choroba srdeční je hlavní příčinou morbidity a mortality ve vyspělých zemích. Je proto pochopitelné, že zájem experimentálních a klinických kardiologů se v průběhu uplynulých 45 let soustředil na studium možného snížení rozsahu ischemického postižení srdečního svalu. Bylo zjištěno, že klíčovou roli v určení rozsahu ischemicko/reperfuzního (I/R) poškození hraje porucha funkce mitochondrií, zvláště pak otevření mitochondriálního póru (mPTP). Adaptace na chronickou hypoxii dlouhodobě významně zvyšuje odolnost srdečního svalu k I/R poškození; tento protektivní efekt je doprovázen stabilizací hypoxií-indukovaného faktoru 1alfa (HIF-1alfa). Cílem projektu je proto zjistit, zda stabilizace HIF-1alfa je klíčovým mechanismem zvýšené odolnosti srdce k I/R poškození a analyzovat vliv geneticky a funkčně změněných hladin HIF-1alfa na funkci mitochondrií, především pak na pravděpodobnost otevření mPTP póru při I/R poškození. Očekávané výsledky by měly přispět k objasnění mechanismů, které se uplatňují v protekci ischemického myokardu.; Ischemic heart disease is the leading cause of mortality in developed countries. It is, therefore, not surprising that both experimental and clinical cardiologists have been focused on effective protection of the heart against ischemia/reperfusion (I/R) injury. It is widely accepted that mitochondrial dysfunction, mainly mitochondrial permeability transition pore (mPTP) opening, plays a major role in cardiac I/R injury. Adaptation to chronic hypoxia is a natural stimulus conferring a long-lasting cardioprotection against I/R. Its cardioprotective effects are associated with stabilization of hypoxia-inducible factor 1alpha (HIF-1alpha). The aim of the present study is, therefore, to determine whether HIF-1alpha stabilization is the key mechanism increasing myocardial tolerance to I/R injury and to analyze the effect of genetically and functionally modified HIF-1alpha levels on mitochondrial function and mPTP opening during I/R injury. These results should contribute to the clarification of mechanisms participating in the protection of the ischemic heart.

• Keywords
• infarkt myokardu, kardioprotekce, myocardial infarction, cardioprotection, Mitochondrie, Mitochondria, chronická hypoxie, hypoxií-indukovaný faktor 1alfa, chronic hypoxia, hypoxia-inducible factor 1alpha,

• NML Publication type
• závěrečné zprávy o řešení grantu AZV MZ ČR