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J Slezák

Publications and source records attributed to J Slezák.

At least 19 recordsLinked to original sources
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↗
PubMed1990

Calcium paradox in the isolated rat-heart--the effects of diltiazem.

The protective effect of calcium entry blockers can be studied advantageously on the model of the calcium paradox, particularly on the basis of the preservation of haemodynamic and biochemical parameters as well as on the structure of the myocardium (Meno et al. 1984). Our aim in this study was to test the protective effect of the recently developed Czechoslovak drug diltiazem (LACHEMA) under conditions of the Ca2+ paradox.

Animals↗
PubMed1990

The effect of calmodulin inhibitors of the adenylate cyclase system.

Experiments using a cytochemical method showed the presence of a specific precipitate of the adenylate cyclase (AC) reaction on the sarcolemma and in the subsarcolemmal cisternae and junctional sarcoplasmic reticulum in rat cardiomyocytes. The localization of AC in the given organelles draws attention to the mutual association between Ca2+ ions and cAMP in the modulation of cardiac contractions. Trifluoperazine (TFP) and chlorpromazine (CHP) are known as phenothiazine derivatives inhibiting cellular enzymatic processes dependent on calmodulin and Ca2+. AC is one of these enzyme systems. The administration of TFP and CHP (both in a dose of 0.1 and 3 mmol.1(-1)) did not affect the cytochemical localization of the enzyme. Quantitative determination of 125I-cAMP by RIA showed that CHP inhibited AC activity in both concentrations. TFP, on the other hand, did not inhibit AC activity in 0.1 mmol.1(-1) concentration and actually stimulated its activation in 3 mmol.1(-1) concentration. The different action of the phenothiazine derivatives on AC activity can be attributed partly to the different affinity of TFP and CHP for calmodulin and partly to interaction of the inhibitor-calmodulin complex with the phosphodiesterase (PDE) system.

Adenylyl Cyclase Inhibitors↗
PubMed1990

Mechanism of action of estradiol on sodium pump in sarcolemma from the myocardium.

Today it is accepted that estrogens mitigate the consequences of ischemic heart disease. Preliminary experiments revealed an increase in heart sarcolemmal (Na+ + K+)-ATPase activity after application of estradiol in vivo. It is also well known the key role of latter enzyme for heart function. The facts mentioned above indicate that estradiol may act on the heart just via modulation of the (Na+ + K+)-ATPase activity. In present paper it is confirmed that 17-beta-estradiol stimulates the activity of sarcolemmal (Na+ + K+)-ATPase by allosteric manner, particularly by increasing positive cooperativity between the K(+)-binding sites of the enzyme. This effect is manifested by enhancement in functional capacity of the sodium pump in sarcolemma. Stimulatory effect of estradiol is bound to integrated myocytes: neither is it manifested in isolated sarcolemma in vitro nor exhibits any influence on the affinity of binding sites for cardiac glycosides or on total capacity of the sarcolemma to bind ouabain. Basing on the data obtained it was assumed that estradiol acts on the (Na+ + K+)-ATPase not directly but by means of a mediator released within the myocyte.

Animals↗
PubMed1990

[Analysis and study of factors in ischemia-reperfusion heart damage].

Specific features of myocardial damage induced by overload and the very action of reactive oxygen species were analyzed and characterized. The experiments were performed on the isolated perfused heart of the rat (according to Langendorff). Overload of the heart by calcium ions was studied on the model of calcium paradox; damage of the heart by reactive oxygen species was induced by a single application of a free radicals generating system. Functional, biochemical, and ultrastructural parameters were studied. Several of the examined parameters (lactate accumulation, drop of total adenine nucleotides, transmural heterogeneity in the histochemical reactivity of enzymes) are of a certain value in recognizing the participation of individual factors involved in reperfusion induced damage of the myocardium.

Animals↗
PubMed1990

[Effect of calcium antagonists on the Ca2(+) paradox].

The model of calcium paradox was used to test the effect of the calcium entry blocker Diltiazem (concentration 4.0 mumol.l-1) and of the calmodulin inhibitor Trifluoroperazin (concentration 1.0 mumol.l-1). Application of each preparation resulted in improved cardiac function manifested by restoration of the electrical and contractile activity and by increased coronary flow. Both Diltiazem and Trifluoroperazin exerted a protective effect on the preservation of enzymatic activities and of ultrastructure in conditions of impaired calcium homeostasis.

Animals↗
PubMed1989

Differences in transmural distribution of cardiomyocyte injury Ca paradox versus postischemic reperfusion phenomenon.

Normothermic, 3 min lasting perfusion of isolated rat heart with Krebs-Ringer-Henseleit solution in which Ca was replaced by EDTA, followed by successive perfusion of Ca2+ containing medium resulted in structural and metabolic derangement of myocardial cells; this could be demonstrated electronmicroscopically and histochemically. Unlike in ischemia, Ca paradox left the enzymes LDH, SDH, beta-HBDH as well as alpha-glucan phosphorylase and ATP-ases better preserved in the subendocardial layer of the left ventricle. Ultrastructural analysis of this phenomenon showed good correlations with the histochemical findings. A large portion of cardiomyocytes in the subendocardial layer showed only slight changes. On the other hand, myocytes in the subepicardial layer were severely injured and all characteristics of the calcium paradox were present including hypercontraction bands with fusion of myofilaments, extrusion and accumulation of oedematous mitochondria containing electron dense material intracristally, sarcolemmal ruptures, separation of intercalated discs etc. The better preservation of the subendocardial region in experiments with calcium paradox could be explained by inadequate perfusion of this layer with Ca2+ free medium due to transmural anatomical inhomogeneity of the capillary supply, resulting in a better protection of these myocytes from Ca paradox. The heterogeneity in transmural distribution of injuries is a multifactorial phenomenon. In addition to factors such as intramural pressure gradient, transmural pressure, enddiastolic intraventricular pressure etc., the most important factors in both types of injuries should be regarded the amount of vascular supply, blood flow and perfusate volume.

Animals↗
PubMed1989

Partial prevention of calcium paradox in isolated perfused rat hearts by diltiazem.

It is well known that excessive calcium entry into the myocardial cells may contribute considerably to damage of the heart caused by postischemic reperfusion. The effect of increased calcium entry on hemodynamics, energy metabolism and histochemically estimated enzyme activities in isolated, perfused (Langendorff) rat heart preparation was investigated using calcium paradox (CaPX) as a model. After a 15 min period of stabilized perfusion of the heart, CaPX was induced at 37 degrees C by 2.5 min lasting calcium depletion (calcium-free perfusion) and subsequent calcium repletion (10 min). Changes induced by CaPX concerned loss of electrical and mechanical activities of the heart, significant decreases in coronary flow and ATP, ADP and the total content of adenine nucleotides in tissue as well as considerable depression in ATPases, SDH, beta-HBDH, LDH and glycogen phosphorylase activities in the myocardium. Diltiazem in concentration of 4.0 mumol.l-1 applied prior to calcium depletion and during calcium repletion prevented partially the deterioration of cardiac function by improving contractility and electrical activity of the heart as well as the coronary flow. The effect of diltiazem in concentration of 0.4 mumol.l-1 was less expressed. After both concentrations of diltiazem used, a better preserved ultrastructure, higher activities of the enzymes investigated, significantly higher ATP and total adenine nucleotide levels were seen in the myocardium as compared to the untreated controls.

Adenosine Triphosphatases↗
PubMed1989

[Transmural differences between damaged cardiomyocytes due to post-ischemic reperfusion and calcium paradox].

Normothermic 3 min lasting perfusion of the isolated rat heart by Krebs--Henseleit solution in which Ca2+ was replaced by EDTA and subsequent perfusion with a Ca2+ containing medium induced structural and metabolic changes demonstrated electron microscopically and histochemically. In contrast to the ischemic reperfusion damage, in calcium paradox, the histochemically studied enzymes alpha-glucan-phosphorylase, lactate dehydrogenase, succinic dehydrogenase, beta-hydroxybutyric dehydrogenase, and ATPases were better preserved in the subendocardial region of the left ventricle. Ultrastructural analysis of this phenomenon showed good correlation with histochemical findings. A large portion of cardiomyocytes in the subendocardial layer exhibited but small changes. On the other hand, myocytes in the subepicardial region and in the midmyocardium were markedly damaged and all characteristic signs of calcium paradox were present, including hypercontraction bands with myofilament fusion, extrusion and accumulation of edematous mitochondria with occurrence of electron dense material in mitochondrial cristae, ruptures of the sarcolemma in all its layers, separation of intercalated discs, etc. The better preservation of the subendocardial region in experiments with calcium paradox is attributable to inadequate perfusion of this region by calcium free medium due to transmural anatomic inhomogeneity of capillary supply whose insufficiency in the subendocardial region results in a better protection of these myocytes from Ca2+ paradox.

Animals↗