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Biomedical subjects

J Styk

Publications and source records attributed to J Styk.

At least 19 recordsLinked to original sources
PubMed1999

Prevention of processes coupled with free radical formation prevents also the development of calcium-resistance in the diabetic heart.

Recently it was shown that besides their negative role in pathogenesis of diabetes, reactive oxygen species (ROS) and particularly the products of non-enzymatic glycation of proteins (NEGP) may also participate in some processes of adaptation of the myocardium to diabetes, such as in the mechanism of development of calcium resistance of the heart. Our study revealed that the hearts of rats with experimentally induced diabetes (single dose of streptozotocin, 45 mg/kg i.v., 6 U/kg insulin daily) develop considerable resistance against calcium overload (induced by means of Ca-paradox). On the day 63 after the beginning of experiment, when the diabetic cardiomyopathy became fully developed but the hearts were still not failing, their calcium resistance was increased to 83.33%. Our results provide evidence that, when applied in a special regimen, resorcylidene aminoguanidine (RAG, 4 mg/kg) prevented both, the formation of fructosamine (a source of ROS generation), and also that of the advanced Maillard products, in the heart sarcolemma of diabetic rats. The effect of RAG was accompanied by a decrease in calcium resistance in the group of rats with chronic diabetes (63 days) from 83.3 to 46.7%. It is concluded that NEGP and ROS formation are inevitably needed for development of calcium resistance in the diabetic hearts.

Animals↗
PubMed1997

Species differences in localization of cardiac cAMP-phosphodiesterase activity: a cytochemical study.

The localization of the membrane-bound cyclic 3',5'-AMP phosphodiesterase in cardiac tissues of both, rat and dog was studied by cytochemical method. 40 microm thick slices from glutaraldehyde fixed heart tissue were incubated in the medium with cAMP as a substrate and Pb ions as a capture metal of the reaction product. The cAMP-PDE activity in the rat ventricle was only shown positive on the sarcolemma. Whereas, in canine ventricular tissue the cAMP-PDE activity in cardiomyocytes was shown on the sarcolemma, on the junctional sarcoplasmic reticulum and on subsarcolemmal cisternae. The results confirm differences in the localization of cAMP-PDE in dog and rat heart.

3',5'-Cyclic-AMP Phosphodiesterases↗
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

Mechanisms that may be involved in calcium tolerance of the diabetic heart.

In diabetes the hearts exhibit impaired membrane functions, but also increased tolerance to Ca2+ (iCaT) However, neither the true meaning nor the molecular mechanisms of these changes are fully understood. The present study is devoted to elucidation of molecular alterations, particularly those induced by non-enzymatic glycation of proteins, that may be responsible for iCaT of the rat hearts in the stage of fully developed, but still compensated diabetic cardiomyopathy (DH). Insulin-dependent diabetes (DIA) was induced by a single i.v. dose of streptozotocin (45 mg.kg-1). Beginning with the subsequent day, animals obtained 6 U insulin daily. Glucose, triglycerides, cholesterol and glycohemoglobin were investigated in blood. ATPase activities, the kinetics of activation of (Na,K)-ATPase by Na+ and K+, further the fluorescence anisotropy of diphenyl-hexatriene as well as the order parameters of membranes in isolated heart sarcolemma (SL) were also investigated. In addition, the degree of glycation and glycation-related potency for radical generation in SL proteins were determined by investigating their fructosamine content. In order to study calcium tolerance of DH in a 'transparent' model, hearts were subjected to calcium paradox (Ca-Pa, 3 min of Ca2+ depletion; 10 min of Ca2+ repletion). In this model of Ca(2+)-overload, Ca2+ ions enter the cardiac cells in a way that is not mediated by receptors. Results revealed that more than 83% of the isolated perfused DH recovered, while the non-DIA control hearts all failed after Ca-Pa. DH exhibited well preserved SL ATPase activities and kinetics of (Na,K)-ATPase activation by Na+, even after the Ca-Pa. This was considered as a reason for their iCaT. Pretreatment and administration of resorcylidene aminoguanidine (RAG 4 or 8 mg.kg-1) during the disease prevented partially the pathobiochemical effects of DIA-induced glycation of SL proteins. DIA-induced perturbations in anisotropy and order parameters of SL were completely prevented by administration of RAG (4 mg.kg-1). Although, the latter treatment exerted little influence on the (Na,K)-ATPase activity, it decreased the calcium tolerance of the DH. Results are supporting our hypothesis that the glycation-induced enhancement in free radical formation and protein crosslinking in SL may participate in adaptive mechanisms that may be also considered as 'positive' and are responsible for iCaT of the DH.

Animals↗
PubMed1996

Diabetic cardiomyopathy in rats: biochemical mechanisms of increased tolerance to calcium overload.

Abundant information is now available about changes in subcellular organelles that are responsible for the impaired intracellular calcium homeostasis in diabetic cardiomyopathy. Some of these changes concern heart sarcolemma and include decrease in the following variables: calcium binding, influx of calcium through the L-type calcium channels, (Na,K)-ATPase activity and its affinity to sodium, Na(+)-Ca2+ exchange, H(+)-Na+ exchange, etc. Diabetic hearts also exhibited increased tolerance to calcium, but none of the above membrane perturbations were clearly identified as the source of this effect. The present study was undertaken in order to identify those alterations appearing in diabetes which are specific for the diabetic heart only. Our interest was focused on changes in sarcolemmal ATPase activities, particularly those of the (Na,K)-ATPase and its activation by increasing concentrations of sodium and potassium. Studies were performed in the acute (8 days) and chronic (63 days) phase of development of insulin-dependent diabetic cardiomyopathy. Wistar rats were made diabetic by administration of streptozotocin. To test the effect of excess calcium, the well-established model of calcium paradox was used. From the results obtained the following conclusions have been made: (a) diabetic hearts exceed normal hearts in their tolerance to calcium overload. In this respect the effect of chronic diabetes is more pronounced than the effect of acute diabetes; (b) the activities of sarcolemmal ATPases in diabetic hearts remain relatively well preserved. For this reason and with respect to modulation of calcium tolerance, the changes in specific properties of the ATPases, particularly those in the (Na,K)-ATPase, outweigh the importance of perturbations in their activities; (c) the enormous decrease in affinity of the (Na,K)-ATPase to sodium (increased K(m) value) monitored in calcium paradox in acute diabetic hearts was absolutely missing in "calcium-tolerant" chronic diabetic hearts. This observation pointed to a possible relation that may exist between the specific properties (Na,K)-ATPase adapted to work in chronic diabetic hearts and the enhanced calcium tolerance of those hearts; (d) the specific mechanism responsible for improved activation of the (Na,K)-ATPase by sodium and also partially responsible for potassium ions, which is clearly manifested in chronic diabetic hearts upon calcium paradox, still remains to be elucidated. Nevertheless, it could be assumed that the same mechanism may be also co-responsible for the enhanced tolerance of diabetic hearts to calcium.

Adenine Nucleotides↗
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↗
PubMed1993

Suppression of reperfusion induced arrhythmias in the isolated rat heart: pretreatment with 7-oxo prostacyclin in vivo.

OBJECTIVE: The aim was to investigate the late effect of pretreatment with 7-oxo prostacyclin on reperfusion induced arrhythmias in the isolated rat heart. METHODS: Forty eight hours after intramuscular administration of drug in vivo (50 micrograms.kg-1 body weight), isolated Langendorff perfused rat hearts were subjected to 30 minutes of regional ischaemia and 5 minutes of reperfusion. Incidence and duration of ventricular arrhythmias in both pretreated and control groups were evaluated on reperfusion. Morphological examination was also performed. RESULTS: In the untreated group reperfusion induced 75% of sustained ventricular fibrillation. Incidence of ventricular fibrillation, its duration, and arrhythmia score were significantly lower in the pretreated group. Pretreatment with 7-oxo prostacyclin had no effect on heart rate and coronary flow throughout the whole course of perfusion. Neither was the occluded zone size affected. Ultrastructure of ischaemic and reperfused myocardium was better preserved in the pretreated group. CONCLUSIONS: Antiarrhythmic action of 7-oxo prostacyclin was unrelated to changes in haemodynamics, thus suggesting the direct influence of the myocardium. The possible mechanism of action may involve maintenance of intracellular cation homeostasis (particularly of Na+ and Ca2+) due to a stimulation of sarcolemmal Na+ pump activity.

Animals↗
PubMed1993

On the role of digoxin-like substances, ANP, and AVP in natriuresis induced by hypertonic saline infusion in dogs.

The increase of sodium concentration in cerebrospinal fluid or in plasma triggers the osmoregulatory mechanism, namely, the enhancement of renal free-water reabsorption and natriuresis. The increase of free-water reabsorption has been recognized for many years as a consequence of the osmotically released vasopressin (AVP). However, the control of renal sodium excretion in the mechanism of osmoregulation has not been clarified It has been suggested to be, at least in part, of hormonal nature, implying the decreased release of aldosterone and the increased release of atrial natriuretic peptide (ANP), digoxin-like substances (DLIS), and AVP. Neither of these factors, however, has been unequivocally linked to the mechanism of immediate natriuresis caused by an acute increase in cerebrospinal fluid or plasma sodium concentration. It was reconfirmed in our present experiments in anesthetized dogs that aldosterone, ANP, and DLIS could hardly play a role in the immediate natriuresis after the i.v. infusion of hypertonic saline (20% NaCl solution infused in 20 min in an amount that was 0.13% of body weight). However, the role of AVP in this type of natriuresis seems more promising as a V1/V2 receptor antagonist applied i.v. before the hypertonic saline loading completely prevented the increase of renal sodium excretion. Natriuresis after the isotonic saline load was not impaired by the same antagonist of vasopressin receptors.

Animals↗
PubMed1993

Evaluation of ischemia-reperfusion injury by malondialdehyde, glutathione and gamma-glutamyl transpeptidase: lack of specific local effects in diverse parts of the dog heart following acute coronary occlusion.

Alterations in the levels of glutathione, glutathione disulfide, malondialdehyde, and the activity of gamma-glutamyl transpeptidase in nonischemic and ischemic parts of the left ventricle and in the right ventricle were studied in canine hearts after occlusion of the left anterior descending coronary artery for 60 minutes and subsequent reperfusion for 20 minutes. Ischemia caused no significant change in malondialdehyde concentration and gamma-glutamyl transpeptidase activity in ischemic or nonischemic parts of the left ventricle, but it increased the activity of gamma-glutamyl transpeptidase in the continuously perfused right ventricle. Reperfusion of the ischemic areas of the left ventricle was accompanied by accumulation of malondialdehyde and an increase in gamma-glutamyl transpeptidase activity, not only in the reperfused and adjacent areas of the left ventricle, but also in the continuously perfused right ventricle. An increase in the level of glutathione disulfide and decrease in glutathione occurred in all parts of the myocardium during coronary occlusion; these changes were maintained in reperfusion. The findings indicate that the effects of acute occlusion and reperfusion of the left anterior descending coronary artery on myocardial concentrations of glutathione, glutathione disulfide and malondialdehyde or gamma-glutamyl transpeptidase activity are not confined to the local area.

Animals↗
PubMed1991

Haemodynamics in the first seconds after coronary artery occlusion.

The changes in cardiac and in total haemodynamics, occurring during the first seconds of occlusion and the subsequent desocclusion of coronary arteries were studied on 28 dogs. The most intensive changes were observed after the trunk occlusion of the left coronary artery. Simultaneously with decreasing blood inflow into the myocardium its contractility and the systolic pressure in the left ventricle and the outflow from the coronary sinus began to fall rapidly. The systolic pressure in the left ventricle decreased within the first 10 s from 24 to 13-15 kPa (180 to 100-110 mm Hg), which means that the systolic pressure fell about 1 kPa (7-8 mm Hg) per second, or 0.5-0.6 kPa (4-5 mm Hg) per systole. At the same time the end-diastolic pressure in the left ventricle also increased from zero to 3-4 kPa (25-30 mm Hg). After the trunk desocclusion of the left coronary artery the systolic pressure in the left ventricle proceeded to fall by about 2-3 kPa (15-22 mm Hg). Only then, 20-25 s after the desocclusion, blood flow in the left coronary artery began to rise intensively and 4-6 s later the myocardial contractility and the systolic pressure in the left ventricle also increased. After unclamping (50-60 s), there was an overshoot of haemodynamic values above preocclusive values and then followed the compensatory phase. This phase lasted 80-90 s and on its peak the pressure and flow parameters increased by about 50-60% above preocclusive values. During the occlusion of ramus interventricularis anterior or ramus circumflexus for 30-60 s the haemodynamic parameters changed only slightly. The same was observed during trunk occlusion of the right coronary artery (30-60 s), but in that case many extrasystoles occurred.

Animals↗
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↗
PubMed1991

[Right-sided mechanical circulatory support in acute right ventricular failure in the dog].

The technique of surgically induced acute progressive right ventricular failure in experimental animals is described. It sumultates the hemodynamic situation of right ventricular failure in some patients after termination of extracorporeal circulation applied for carrying out procedures on the left ventricle. The described technique consists of rightsided longitudinal ventriculotomy, destruction of the tricuspid valve, and ligation of the right coronary artery. Nine control dogs died within two hours after induction of failure due to low stroke volume caused by low pulmonary and left atrial pressure. The use of rightsided support appliance draining blood from the right atrium in systole and pumping it into the trunk of the pulmonary artery in diastole by means of a membrane pump resulted in further 12 dogs in the restoration of left ventricular diastolic pressure, significant increase of aortal pressure (p less than 0.003) and stroke volume (p less than 0.003) and in a decrease of right atrial pressure (p less than 0.003). The study demonstrated that by using the described mechanical support the circulation can be adequately assisted so that the failing right side of the heart can get restored. (Tab.1,Fig.5,Ref.25.).

Acute Disease↗
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↗