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Cardioprotective action of remote ischemic perconditioning in rats
Chalupová, Miloslava ; Neckář, Jan (advisor) ; Žaloudíková, Marie (referee)
Remote ischemic perconditioning (RIPerC) stimulated by brief nonlethal periods of ischemia and reperfusion of a remote organ or a tissue applied during myocardial infarction, is a powerful cardioprotective maneuver. Because of its easy realization, for example, through inflation and deflation of blood pressure cuff, this method has a big potential for translation to clinical settings. The main purpose of this thesis was to investigate the cardioprotective effect of RIPerC as a reduction of infarct size and the incidence and severity of ischemic and reperfusion arrhythmias and to examine, whether this protective effect will be confirmed also in rats with partial deletion of a transcriptional factor of hypoxia-inducible factor-1α (HIF-1α). HIF-1α is a main regulator of hypoxic intracellular signalization and its role was previously indicated in cardioprotection by local ischemic preconditioning. Anesthetized rats were subjected to 20 minutes of the left anterior descending coronary artery occlusion followed by 3 hours of reperfusion. RIPerC was performed by 3 cycles of 4 minutes of ischemia and 2 minutes of reperfusion with a pressure cuff placed on both hind-limbs. This study shows that RIPerC failed to induce protection in any observed factors of ischemia-reperfusion heart injury. Key words: heart,...
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Cardioprotective role of epoxyeicosatrienoic acids in ischemia-reperfusion injury.
Veselá, Barbora ; Neckář, Jan (advisor) ; Kolář, David (referee)
Epoxyeicosatrienoic acids (EETs) are arachidonic acids metabolites that importantly contribute to vascular and cardiac physiology and pathophysiology. Current research in the field of EETs shows that these molecules can significantly reduce the rate of acute ischemia- reperfusion injury of the heart. However, they can also contribute significantly to the recovery of the heart muscle following myocardial infarction and to reduce the development of post- ischemic heart failure. The project aims to outline the known cardioprotective effect(-s) of EETs on myocardial ischemia/reperfusion injury and their mechanisms. Key words: heart, ischemia-reperfusion, epoxyeicosatrienoic acids
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The effect of methadone on cardiac ischemic tolerance in rats
Mošovská, Linda ; Neckář, Jan (advisor) ; Říha, Hynek (referee)
Opioids are considered as a dangerous addictive substances which are widely used in medicine for their strong analgetic effects. Opioids (such as morphine and methadon) may nevertheless play an important role in the resistance of the heart to ischemia by reducing the rate of cell damage. This protective effect is well understood about morphine but we don't know almost nothing about effects of methadone on the myocardium. The main aim of this thesis was to find out how chronic methadone treatment affects ischemic tolerance of rat hearts. For our experiments we used Wistar rats in two series. In the first series we administered morphine (10 mg/kg/day, i.m.) or methadone (2 mg/kg/day, i.m.) for 10 days. In the second experiment series we administered methadon for 28 days (2 mg/kg/day, i.m.). For analysis of the ischemic heart tolerance we used the isolated perfused heart method. Incidence and severity of ischemia and reperfusion arrhythmias were analyzed during the 50 min of ischemia and early reperfusion. Infarct size was analyzed histochemically, using tetrazolium salts and KMnO4 1 h after reperfusion and was determined by planimetric method. In the first series of experiments analyzing the effect of 10-day administration of both opioids on the resistance of the heart to ischemia we did not find a...
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Effect of erythropoietin on myocardial ischemic tolerance
Jindrová, Helena ; Kolář, František (advisor) ; Žurmanová, Jitka (referee)
Adaptation to chronic hypoxia increases myocardial resistance to acute ischemia/reperfusion (I/R) injury, similarly to application of exogenous erythropoietin (EPO). Nevertheless, it is not known if EPO induced by chronic hypoxia plays a role in its cardioprotective mechanism. The aim of this study was to find out if protective effect of exogenous EPO adds up to protection offered by chronic hypoxia. Adult male mice (ICR) were adapted to intermittent hypobaric hypoxia 8 hours per day, 5 days per week for 5 weeks. The degree of hypoxia corresponded to 7000 metres. Control animals were housed for the same time in normoxic environment. Resistance to I/R injury was assessed according to size of myocardial infarction induced by 45-min global ischemia and 1-h reperfusion of the heart in vitro. Animals were treated 24 h before the experiment with 200 or 5000 U/kg EPO. Treatment with 200 U/kg EPO was sufficient to significantly limit infarct size in normoxic animals (33,56 ± 2,93 % vs. 25,71 ± 2,29 %). Hypoxic adaptation decreased infarct area to 23,49 ± 2,30%, but additive effect of EPO in hypoxic group was not detected. The results indicate that exogenous EPO employs the same cardioprotective mechanisms as adaptation to chronic intermittent hypoxia. Preliminary results indicate that repeated application of EPO...
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The effects of dexrazoxane on ischemia-reperfusion injury in rat heart
Boudíková, Adéla ; Neckář, Jan (advisor) ; Hloušková, Patricie (referee)
Dexrazoxane (DEX) is clinically used to reduce cardiotoxic efects of anthracycline cytostatics. Its cardioprotective efect is caused by chelatation of free iron and defends myocard against dangerous hydroxyl radicals. This research finds out how dexrazoxane works in ischemic-reperfusion damages of rat's heart. Each rat was infused by DEX (50, 150, 450 mg/kg) or by control solution. Isolated perfused rat's hearts were exposed to local ischemia for 30 minutes than 10 minutes of reperfusion for studing ischemic arrhythmias followed by 15 minutes of local ischemia and 10 minutes of reperfusion to examine reperfusion arrhythmias. For evaluation of EKG (ventricular arrhythmias) was used software CAR and Lambeth convention. Global ischemias (15 min.) were induced in rat's hearts (DEX 150 mg/kg) and left ventricules were used for HPLC to determinate concentration of glutathion. In vivo experiments rats were infused by DEX 50, 150 mg/kg or control solution and were exposed for 20 minutes to local ischemia and for 3 hours to reperfusion. Infarct size was evaluated based on the cross section of heart (GIMP, Ellipse). Maximum total number of ischemic arrhytmias decreased by DEX 150 mg/kg (64% comparing to controls). Reperfusion score was reduced by DEX 150 to 48% and percents of ventricular fibrilation was...
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