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Biomedical subjects

J Slezák

Publications and source records attributed to J Slezák.

At least 19 recordsLinked to original sources
PubMed1999

Free oxygen radicals contribute to high incidence of reperfusion-induced arrhythmias in isolated rat heart.

Early period of reperfusion of ischemic myocardium is associated with a high incidence of severe tachyarrhythmias including ventricular tachycardia and fibrillation (VT and VF). Free oxygen radicals (FOR) have been identified as one of the principal factors responsible for reperfusion-induced events. However, their role in arrhythmogenesis is not clear. In the present study, in isolated Langendorff-perfused rat hearts subjected to 30 min global ischemia, the onset of reperfusion induced 100% incidence of both VT and VF with their gradual cessation over 5 min of reperfusion. Generation of H2O2 in the myocardium in the first minutes of reperfusion was visualized by means of cerium cytochemistry and confirmed by X-ray microanalysis. The mechanism of the arrhythmogenic effect of FOR may involve inhibition of the sarcolemmal Na+/K+-ATPase, as demonstrated in the rat heart sarcolemmal fraction subjected to FOR-generating system (H2O2 + FeSO4).

Animals↗
PubMed1997

Cytochemical and immunocytochemical localization of Na,K-ATPase alpha subunit isoenzymes in the rat heart.

In order to understand the functional significance of Na,K-ATPase subunits as well as their isoenzymes, a precise subcellular localization of these in the myocyte is a crucial prerequisite. Cytochemical, immunofluorescence, preembedding immunogold and horse radish peroxidase-diaminobenzidine methods, demonstrated alpha 1 isoenzyme immunoreactivity on the sarcolemma, T-tubules and the subsarcolemmal cisterns of the adult cardiac myocytes. Cytochemically, ouabain resistant Na,K-ATPase precipitate was localized only in the subsarcolemmal cisterns and junctional sarcoplasmic reticulum. For alpha 2 isoenzyme, immuno-reactivity was demonstrated on the sarcolemma as well as in all areas of the myocytes in particularly a close proximation to the sarcoplasmic reticulum and microsomes. For alpha 3 isoenzyme, only a weak insignificant signal was noted on the sarcolemma, intercalated disc and sarcoplasm. It is suggested that cytochemical ouabain resistant precipitate present in subsarcolemmal cisterns and junctional sarcoplasmic reticulum represent alpha 1 isoenzyme of Na,K-ATPase. A differential as well as unique localization of alpha subunit isoenzymes of Na,K-ATPase in specific structures of cardiac myocytes may suggest importance in physiological function at these sites.

Animals↗
PubMed1997

Estradiol modulates the sodium pump in the heart sarcolemma.

Cardiovascular effects of estrogens and particularly that of estradiol involve protection of the heart against ischemia. These effects were believed to be mainly indirect, mediated via changes in the blood and blood vessels. In the present paper a direct action of estradiol on the heart is demonstrated. Estradiol stimulates (p < 0.001) the Na,K-ATPase activity of cardiac sarcolemmal membranes by stimulating in an allosteric manner, the activation of the enzyme by potassium. The latter activation involves also an increase in affinity to potassium of the potassium binding sites on the enzyme molecule, but remains without any effect on the capacity and KD value of specific ouabain binding to the Na,K-ATPase. Estradiol is also antagonizing the depression of Na,K-ATPase activity that may be caused by ischemia and it is stimulating (p < 0.01) the ouabain-sensitive uptake of 86Rb into the heart cells. Our results indicate, that in addition to the known indirect effects of estradiol on the heart, the hormone also stimulates the activity and improves the kinetics of interaction of cardiac sarcolemmal Na,K-ATPase with ATP as well as with Na+ and K+ ions. This direct action may also account for the cardioprotective effects of estradiol.

Adenosine Triphosphate↗
PubMed1997

Adriamycin depresses in vivo and in vitro phosphatidylethanolamine N-methylation in rat heart sarcolemma.

Adriamycin, an effective anticancer chemotherapeutic agent, causes an insidious and delayed cardiotoxicity. Different subcellular abnormalities including calcium transport changes in the sarcolemma (SL) as well as downregulation of the adrenergic system have been shown to be associated with the development of this cardiomyopathy. Since both of these activities are influenced by phospholipid methylation, effects of adriamycin on the three catalytic sites of SL phosphatidylethanolamine N-methyltransferase were examined. Rats were administered with a cumulative dose of adriamycin (15 mg/kg) over 2 weeks and examined after 3 weeks. Vehicle injected animals served as controls. Dyspnea, high mortality rate, ascites and decrease in aortic and left ventricular systolic pressure, as well as increase in left ventricular end diastolic pressure were seen in the adriamycin group. Myocardial cell damage typical of adriamycin cardiomyopathy, i.e. sarcotubular swelling, vacuolization and myofibrillar drop-out, was also apparent. Total methyl group incorporation into SL phosphatidylethanolamine using radiolabeled S-adenosyl-L-methionine as the donor was significantly depressed in the 3 week group at catalytic sites II and III. Decreased production of methylated intermediates, phosphatidyl-N-monomethylethanolamine and phosphatidyl-N,N-dimethylethanolamine as well as phosphatidylcholine (PC) was seen. Depression of phosphatidylethanolamine N-methylation was also noticed when SL, isolated from untreated hearts, was exposed in vitro to different concentrations (10, 100 and 1000 microM) of adriamycin. Inhibition of phosphatidylethanolamine N-methylation appears to be mediated by adriamycin-induced increase in the oxidative stress and may contribute in the pathogenesis of subcellular changes associated with this cardiomyopathy.

Analysis of Variance↗
PubMed1996

Cytochemical distribution of cyclic AMP-dependent 3',5'-nucleotide phosphodiesterase in the rat myocardium.

The cytochemical localization of cAMP-dependent phosphodiesterase was studied in the rat myocardium. Slices 40 microns thick from perfusion-fixed rat hearts were incubated in the medium with cAMP as a substrate and Pb ions as a capture metal of the reaction product. After the incubation in the basic medium the specific precipitate of cAMP phosphodiesterase was localized on the sarcolemma of cardiomyocytes. In addition, it was localized on the plasmalemma of endothelial cells of capillaries and small coronary arteries as well as on the membrane of smooth muscle cells. Using selective inhibitors SK&F 94120 for phosphodiesterase III and Rolipram for the IV isoenzyme, both isoforms were detected on the membrane of smooth muscle cell. In addition, phosphodiesterase III was localized on the sarcolemma only and phosphodiesterase IV on the sarcolemma of cardiomyocytes and the plasmalemma of endothelial cells.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Diabetic cardiomyopathy in rats: alleviation of myocardial dysfunction caused by Ca2+ overload.

There is some evidence that diabetic hearts are more resistant to ischaemia/reperfusion injury due to alterations in Ca2+ handling. Our objective was to explore this hypothesis in the model of Ca2+ overloaded heart (calcium paradox, CaP). Diabetes was induced by streptozotocin (45 mg/kg, i.v.). Despite regular insulin treatment blood glucose was increased. After a diabetes duration of 9 weeks the heart/body weight ratio was higher than in age-matched controls, and the heart rate, the coronary flow (CF) and the rate of contraction and relaxation was reduced as assessed in Langendorff preparation. Depressed function was accompanied by a lower content of high energy phosphates and ultrastructural alterations, such as an increased number of glycogen granules, lipid droplets and changes in the walls of capillaries leading to the narrowing of their lumen. In controls, readmission of Ca2+ into Ca(2+)-depleted hearts resulted in extensive deterioration of heart function, development of contraction bands, ultrastructural damage and loss of ATP. Diabetic hearts, despite impaired performance before CaP, showed an improved recovery of heart function manifested by restoration of electrical and contractile activity, as well as CF after Ca2+ repletion. This corresponded to better maintenance of energy metabolism and preservation of ultrastructure. In conclusion, diabetic hearts exhibit greater resistance to Ca2+ overload. Depressed heart function may account for this protective effect: bradycardia facilitates saving ATP; lower CF results in a slower rate of Ca2+ washout from the heart during Ca2+ depletion thus causing less damage to the cell membrane and maintenance of its integrity.

Adenine Nucleotides↗
PubMed1996

Resistance of diabetic rat hearts to Ca overload-related injury. Histochemical and ultrastructural study.

The enzymatic histochemical and ultrastructural alterations of the rat heart during development of streptozotocin (STZ) induced diabetic cardiomyopathy were studied. Moreover, the response of the isolated diabetic hearts to Ca overload-Ca paradox-was investigated. In the early stage of diabetes (1 week of diabetes), no apparent histochemical changes were observed but gentle alterations of the ultrastructure of the myocytes and particularly capillaries were found. Structural changes of the myocytes and microangiopathy accompanied by decreased activities of some enzymes (phosphorylase, various dehydrogenases, ATPase) progressed with time and were more pronounced late in diabetes (9 weeks). Ca paradox induced severe structural damage of the majority of cardiomyocytes and loss of the cellular integrity, and marked decrease in activities of all enzymes. However, in acute diabetic heart only partial Ca paradox was observed. It was manifested by transmural heterogeneity of structural and enzymatic histochemical changes. Evident preservation of the ultrastructure and enzyme activities of the myocardium was revealed in late stage (9 weeks) of diabetes. It can be concluded that diabetes results in prevention of the Ca overload in rat myocardium in vitro. Disturbances in coronary perfusion associated with microangiopathy as well as altered Ca handling and depressed heart function may account for delayed development of Ca paradox in diabetic heart.

Animals↗
PubMed1994

Reversal effects of several Ca(2+)-entry blockers, neuroleptics and local anaesthetics on P-glycoprotein-mediated vincristine resistance of L1210/VCR mouse leukaemic cell line.

The ability of several Ca(2+)-entry blockers, neuroleptics and local anaesthetics to depress the P-glycoprotein-mediated resistance to vincristine was studied in vitro using the L1210/VCR cell line. This cell line was obtained by long-term adaptation of the L1210 mouse leukaemic cell line on vincristine and showed an overexpression of P-glycoprotein and accompanying multidrug resistance (MDR) which was defined as a cell resistance to several cytostatics such as vincristine, vinblastine and actinomycin D. Efficiency of the drugs applied to reverse this resistance was as follows: for Ca(2+)-entry blockers: verapamil (VER) > or = galopamil (GAL) > flunarizine (FLU) >> diltiazem (DIL) > nimodipine (NIM) > or = nifedipine (NIM); for neuroleptics: trifluoperazine (TFP) > chlorpromazine (CHP) > thioridazine (TRD) > perphenazine (PER); for local anaesthetics: carbanilate-Ca7 > cinchocaine (CIN) >> carbanilate-Ca3 > articaine (ART) > carbanilate CAO > lidocaine (LID). Quaternary cabanilate derivatives (Ca7Q and Ca3Q) with permanent positive charge were found to be unable to reverse the vincristine resistance of L1210/VCR cells. No reasonable correlation between the ability of calcium-entry blockers (DIL, VER, GAL, NIF, NIM and FLU) to reduce the viability of L1210/VCR cells growing in the medium supplemented with vincristine and their reported affinity to the L-type of calcium channel was observed. On the other hand, significant positive correlations were observed between both the inhibitory action of local anaesthetics on propagation of action potential in rat sciatic nerve and the ability of drugs to interact with calmodulin and the ability of the respective drug to reverse the resistance of L1210 cells to vincristine.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Overcoming of vincristine resistance in L1210/VCR cells by several corticosteroids. Collateral sensitivity of resistant cells.

Five corticosteroids were tested to determine whether they are able to overcome the multidrug resistance of vincristine resistant mouse leukemia cells L1210/VCR. The most effective in reversing multidrug resistance were cortisone and dexamethasone, less effective as reversing agents were 11-deoxycorticosterone, 1-dehydrocortisone and hydrocortisone. By testing of collateral sensitivity of vincristine resistant cell line to these corticosteroids it was found that only 11-deoxycorticosterone and dexamethasone were toxic to multidrug resistant cells at doses much lower than required for toxicity to the drug-sensitive L1210/S cells. Using thin layer chromatography the polarity of tested corticosteroids was estimated, and good correlation was found between polarity of corticosteroids and their increased toxicity to vincristine resistant cells.

17-Hydroxycorticosteroids↗
PubMed1993

[Late postoperative complications after primary treatment of aortic coarctation].

During the period between 1963 and 1988, 343 patients were operated due to aortic coarctation. 14 patients (4%) were necessarily reoperated for late postoperative complications. In 3 cases (0.8%) reoperation was indicated due to the development of aneurysm in the region of primary operation of aortic coarctation. The development of aneurysm is prevalently predisposed by Vosschulte's indirect aortoplastic operation by the use of a synthetic patch. In the remaining 11 patients (3.2%) the reoperation was indicated owing to the development of recoarctation. Today recoarctation concerns children which were operated under the age of two. The most important moment favourable for the recoarctation development is the secondary constriction of the repaired region in consequence of the coarctation listel fibroid tissue and owing to the incapability of the anastomosis to grow. The perspective rests on using new suture material and combined techniques. Late postoperative complications which follow operations performed due to aorta coarctation remarkably augment the peri and postoperative mortality. Three cases out of the given group of 14 patients terminated by exitus (21%). Hence, it is necessary to remove all moments of predisposition creating a condition favourable for the development of recoarctation and aneurysm. (Tab 2, Fig. 1, Ref. 14.).

Adolescent↗
PubMed1992

[Detection of mitochondrial contact sites and creatine kinase activity in Ca(2+)-stimulated rat hearts].

Contact sites are created by fusion of the inner and outer mitochondrial membrane. They represent a dynamic microcompartment for creatine kinase activity. In this microenvironment the active sites of creatine kinase, oxidative phosphorylation, and ADP/ATP transport interact during basal and stimulated metabolism. Electron microscopic studies showed that the occurrence rate of contact sites was changing according to the energy state of the mitochondrion (Biermans et al., 1989). The aim of this study was to stimulate the metabolism of the rat heart by extracellular calcium and to investigate the formation of contact sites and creatine kinase activity. Isolated rat hearts were perfused with Krebs-Henseleit solution containing 1.6 mmol Ca. After 15 min stabilization the hearts were subjected to 0.6, 0.9, 1.8, 2.2, 2.6, or 3.6 mmol Ca for a period of 15 min. Stimulation of the isolated rat hearts with increasing calcium concentrations was physiologically manifested by enhanced dp/dt and LVP values. A higher frequency rate of mitochondrial contact sites was observed and these were associated with higher creatine kinase activity. We suppose that induction of contact site formation is related to the functional activity of the Ca stimulated rat heart and thus efficient production and transport of energy is provided. (Tab. 1, Fig. 6, Ref. 18.).

Animals↗
PubMed1992

[Endarterectomy of the coronary arteries].

The authors analyze 50 patients with endarterectomy of the coronary arteries during the periods of 1972-1974 and 1988-1990. The results of endarterectomy of the right and left coronary artery provide evidence of its justification in indicated cases whereby contrary to some departments the results of endarterectomy of the left coronary artery are comparable with endarterectomy of the right coronary artery.

Coronary Disease↗
PubMed1991

Functional changes in isolated rat heart related to different factors of reperfusion damage.

The role of ischemia itself, calcium overload and of reactive oxygen species (ROC) in reperfusion injury of the heart was characterized from the physiological, biochemical and morphological point of view. Experiments were performed on isolated rat hearts (Langndorff preparation), perfused at constant pressure of 65 Torr and 37 degrees C. The effect of ischemia was studied on the model of 30 min normothermic global ischemia with consequent 30 min reperfusion. Calcium overload and damage by ROS were modelled by Ca(2+)-paradox (3 min Ca(2+)-depletion followed by 10 min Ca(2+)-repletion) and by intraaortal bolus application of ROS-generating system (H2O2 + FeSO4) respectively. Evaluation of functional and biochemical parameters revealed that the changes in electrical activity, accumulation of lactate and the loss in total adenine nucleotides content in heart tissue may be well applied to characterize the participation of the above mechanisms on total reperfusion damage to the heart. Histochemically detected different patterns of distribution of enzyme activities also allow to distinguish between alterations caused by different factors of reperfusion injury.

Animals↗
PubMed1991

Vulnerability of specialized conductive tissue to ischemia and reperfusion related injury.

The fine structural alteration and histochemical changes of the cardiac conduction system were studied in dogs and rats using various models of ischemic and reperfusion injury. The role of Ca2+ overload and reactive oxygen species (ROS) per se were also investigated. In all models of injury the activity of glycogen phosphorylase (histochemical indicator of the early ischemic changes) was present in nodal and conducting cells, although it was markedly diminished or absent in surrounding contractile muscle. Fine structural ischemic alterations progressed more slowly in conducting cells in comparison with working myocardial cells. Changes induced by Ca2+ paradox or ROS were reversible in conducting tissue in contrast to working myocardial tissue. The observations support the concept that conducting cells are more resistant to ischemia and also to reperfusion related injury than contractile myocardial cells.

Animals↗
PubMed1990

Transmural non-homogeneity of calcium-induced heart injury.

The Ca paradox resulted in marked inhibition, up to disappearance, of histochemically studied enzyme activities (SDH, LDH, beta-HBDH, phosphorylase and ATPase) in the subepicardial layer of the myocardium. In the subendocardial region there was only a small decrease. These transmural differences correlated well with ultrastructural changes. It is assumed that the heterogeneity in transmural distribution of injury is the result of transmural differences in coronary flow.

Adenosine Triphosphatases↗