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J Styk

Publications and source records attributed to J Styk.

At least 19 recordsLinked to original sources
PubMed2005

Ischemia-reperfusion injury--antiarrhythmic effect of melatonin associated with reduced recovering of contractility.

The effect of melatonin on reperfusion arrhythmias and postischemic contractile dysfunction was studied in the isolated rat heart. 25 min global ischemia was induced and followed by 30 min of reperfusion. Melatonin (10 micromol/l) was present in the perfusion solution during the whole experiment. Experiment revealed protective effect of melatonin on reperfusion-induced arrhythmias--arrhythmia score was significantly lower as well as the total time of arrhythmias duration was significantly shorter in melatonin group than in controls. On the other hand, post-ischemic recovering of contractility was significantly reduced in melatonin group.

Animals↗
PubMed2005

The role of NO in ischemia/reperfusion injury in isolated rat heart.

UNLABELLED: Nitric oxide (NO) is an important regulator of myocardial function and vascular tone under physiological conditions. However, its role in the pathological situations, such as myocardial ischemia is not unequivocal, and both positive and negative effects have been demonstrated in different experimental settings including human pathology. The aim of the study was to investigate the role of NO in the rat hearts adapted and non-adapted to ischemia. Isolated Langendorff-perfused hearts were subjected to test ischemic (TI) challenge induced by 25 min global ischemia followed by 35 min reperfusion. Short-term adaptation to ischemia (ischemic preconditioning, IP) was evoked by 2 cycles of 5 min ischemia and 5 min reperfusion, before TI. Recovery of function at the end of reperfusion and reperfusion-induced arrhythmias served as the end-points of injury. Coronary flow (CF), left ventricular developed pressure (LVDP), and dP/dt(max) (index of contraction) were measured at the end of stabilization and throughout the remainder of the protocol until the end of reperfusion. The role of NO was investigated by subjecting the hearts to 15 min perfusion with NO synthase (NOS) inhibitor L-NAME (100 mmol/l), prior to sustained ischemia. At the end of reperfusion, LVDP in the controls recovered to 29.0 +/- 3.9 % of baseline value, whereas preconditioned hearts showed a significantly increased recovery (LVDP 66.4 +/- 5.7 %, p < 0.05). Recovery of both CF and dP/dt(max) after TI was also significantly higher in the adapted hearts (101.5 +/- 5.8 % and 83.64 +/- 3.92 % ) as compared with the controls (71.9 +/- 6.3 % and 35.7 +/- 4.87 %, respectively, p < 0.05). NOS inhibition improved contractile recovery in the non-adapted group (LVDP 53.8 +/- 3.1 %; dP/dt(max) 67.5 +/- 5.92 %) and increased CF to 82.4 +/- 5.2 %. In contrast, in the adapted group, it abolished the protective effect of IP (LVDP 31.8 +/- 3.1 %; CF 70.3 +/- 3.4 % and dP/dt(max) 43.25 +/- 2.19 %). Control group exhibited 100 % occurrence of ventricular tachycardia (VT), 57 % incidence of ventricular fibrillation (VF) - 21 % of them was sustained VF (SVF); application of L-NAME attenuated reperfusion arrhythmias (VT 70 %, VF 20 %, SVF 0 %). Adaptation by IP also reduced arrhythmias, however, L-NAME in the preconditioned hearts increased the incidence of arrhythmias (VT 100 %, VF 58 %, SVF 17 %). IN CONCLUSION: our results indicate that administration of L-NAME might be cardioprotective in the normal hearts exposed to ischemia/reperfusion (I/R) alone, suggesting that NO contributes to low ischemic tolerance in the non-adapted hearts. On the other hand, blockade of cardioprotective effect of IP by L-NAME points out to a dual role of NO in the heart: a negative role in the non-adapted myocardium subjected to I/R, and a positive one, due to its involvement in the mechanisms of protection triggered by short-term cardiac adaptation by preconditioning.

Animals↗
PubMed2004

[Melatonin and the heart].

Evidence gathered during the last years shows that the pineal hormone melatonin participates in the regulation of the heart. Melatoninergic receptors were found in the heart and vessels and also in the higher centers involved in the regulation of cardiovascular system. Melatonin protects the heart against ischaemia-reperfusion injury and also against cardiotoxic effects of adriamycin and alloxan. Lack of melatonin was repeatedly reported in patients with coronary heart disease. Intake of this hormone leads to decrease of blood pressure in normotensive and hypertensive subjects, while pinealectomy induces hypertension. In addition melatonin can probably influence the levels of intracellular calcium in cardiomyocytes. The aim of this review is to summarize available evidence about effects of melatonin on the heart. Mechanisms involved in these effects are also suggested.

Animals↗
PubMed2004

Proteins released from liver after ischaemia induced an elevation of heart resistance against ischaemia-reperfusion injury: 2. Beneficial effect of liver ischaemia in situ.

We have shown earlier that proteins released from the heart during preconditioning may protect non-preconditioned heart during sustained ischaemia, similarly as preconditioning itself. In other our experiments we have documented that also proteins released from isolated rat liver during reperfusion after global ischaemia performed a protective effect on isolated rat heart against ischaemia-reperfusion injury. In the current study we examined the effect of liver ischaemia in situ on resistance of rat heart to ischaemia and reperfusion injury. Wistar rats (male) were subjected to liver ischaemia maintained by occlusion of portal vein and hepatic artery for 20 min, followed with 30-min reperfusion after reopening of both vessels. Then the hearts were isolated and perfused according to Langendorf. Hearts, after initial stabilisation (15 min), were subjected to 20-min ischaemia and 30-min reperfusion. During reperfusion, the haemodynamic parameters of hearts were measured. The protein pattern of high soluble fraction (HS fraction) isolated from rat blood by precipitation with ammonium sulphate was detected by SDS-PAGE. Our results showed improved parameters of pressure and contractility in the group after liver ischaemia (ischaemic group), presented by decreased diastolic pressure and increased LVDP((S-D)) in comparison with levels of these parameters in the control group. We also observed improved heart contraction-relaxation cycles parameters (dP/dt)(max) and (dP/dt)(min) in ischaemic group as compared with the control group. On the other hand, there were no significant differences in heart rate and coronary flow between both experimental groups. SDS-PAGE showed changed protein pattern in HS fraction, particularly the levels of several low molecular weight proteins increased. We conclude that liver ischaemia induced a higher resistance of heart against ischaemia-reperfusion injury. We propose that release of some cardioprotective proteins present in HS fraction can also contribute to this cardioprotection.

Animals↗
PubMed2003

Effect of melatonin on the isolated heart in the standard perfusion conditions and in the conditions of calcium paradox.

UNLABELLED: The effect of melatonin (MLT) on the isolated rat heart was studied using the standard perfusion conditions (Langendorff preparation) and model of calcium paradox (Ca(2+)-paradox). Ca(2+)-paradox was induced by 1 minute perfusion with Ca(2+)-free Krebs-Henseleit (KH) solution and subsequent 20 minutes perfusion with a normal Ca(2+)-containing KH solution. In MLT group, MLT (10 micromol/l) was in the perfusion solution throughout the experiment. In controls, there was no MLT. VARIABLES: heart rate, coronary flow, systolic and diastolic pressure, +dP/dt max (index of contractility) and -dP/dt max (index of relaxation) were measured at the end of stabilization, i.e. after 30 minutes of standard perfusion and then in the 5th, 10th, 15th, 20th minute after perfusion with Ca(2+)-free KH solution. RESULTS: There was no difference between MLT group and controls in the standard perfusion conditions at the end of stabilization. After perfusion with Ca(2+)-free KH solution, systolic-diastolic difference (in the 10th, 15th, 20th minute), +dP/dt max (in the 5th, l0th, 15th, 20th minute) and -dP/dt max (in the 15th minute) were significantly decreased in MLT group in comparison to controls. CONCLUSION: Melatonin didn't influence rat isolated heart in standard perfusion conditions but it made the heart more susceptible to Ca(2+)-paradox.

Animals↗
PubMed2003

Proteins released from liver after ischaemia induced an elevation of heart resistance against ischaemia-reperfusion injury: 1. Beneficial effect of protein fraction isolated from perfusate after ischaemia and reperfusion of liver.

OBJECTIVES: Numerous mechanisms have been proposed to participate in adaptation of heart to ischaemia by ischaemic preconditioning. We have described previously a release of cardio-protective protein fraction during ischaemic preconditioning of dog heart. In the current study the effect of high soluble protein fraction (HS fraction) released from isolated perfused rat liver after ischaemia and reperfusion was examined on isolated perfused rat heart during ischaemia-reperfusion injury. METHODS: Livers were subjected to 30 or 60 min ischaemia followed with 120 min reperfusion. HS fraction was isolated using ammonium sulphate precipitation and dissolved in perfusion solution before Langendorf perfusion of isolated rat hearts. The protein pattern of HS fraction was detected with SDS-PAGE and western blot with ConA and anti ConA antibody. Hearts were then subjected to 20 min ischaemia followed by 20 min reperfusion. During reperfusion, the haemodynamic parameters of hearts were measured. Heart levels of adenine nucleotide were measured in HClO4 extracts using HPLC on C18 column. RESULTS: Liver ischaemia induced changes in protein pattern of HS fraction released from the liver during reperfusion period. Particularly, we registered an increase in amount of several low-molecular weight proteins and decreased amount of high-molecular weight proteins. Proteins in this fraction isolated from perfusate after liver ischaemia interact with ConA with lower intensity as proteins isolated from perfusate after control non-ischaemic condition. HS fraction isolated from perfusate after ischaemia and reperfusion of liver had beneficial effect on heart function during 20 min ischaemia and subsequent 20 min reperfusion, documented by: i) decrease of arrhythmia score from 2 to 1 in 5 min of reperfusion and from 2 to 0 in 10 min of reperfusion; ii) improved heart contractility monitored as stabilised [dP/dt]max and increased Q parameter; iii) increased coronary flow. Proteins isolated from liver perfused under control non-ischaemic condition did not induce similar effects. The stabilisation of heart haemodynamics, observed after administration of HS proteins isolated from perfusate after ischaemia and reperfusion was associated with slight increase in ATP and ADP levels as well as decrease in AMP level.

Animals↗
PubMed2002

Energy transfer in acute diabetic rat hearts: adaptation to increased energy demands due to augmented calcium transients.

OBJECTIVES: Hearts of rats with diabetes mellitus (DM) are characterized by energy demands exceeding their energy production, but they might also exhibit decreased vulnerability to ischemia and calcium overload. This indicates adaptation in cardiac energetics (CE), where energy transport is not rate-limiting. Aim-This study was designed to elucidate the functional significance of the DM-induced adaptation in CE by investigating the formation of mitochondrial contact sites (MiCS), facilitating the Ca-dependent/high-capacity energy transfer from mitochondria, in conjunction with testing the ischemic tolerance (IT) of hearts. METHODS: After 1 week of streptozotocin-induced DM (45 mg/kg iv), the hearts of male diabetic and age-matched control rats (C) were isolated and Langendorff-perfused with either 1.6 or 2.2 mmol/L of CaCl(2). MiCS formation was assessed by cytochemical detection of mCPK octamers and was quantified stereologically as MiCS to mitochondrial surface ratio (S(S)). IT was evaluated in anesthetized open-chest animals subjected to 30-min occlusion of the LAD coronary artery followed by 4-h reperfusion, by monitoring ischemic arrhythmias and by measuring the size of infarction (tetrazolium double staining). RESULTS: In C hearts, increasing Ca2+ induced both positive inotropic response (dP/dt increase from 2270 +/- 220 to 2955 +/- 229, p < 0.01) and elevated MiCS formation (S(S) increase from 0.070 +/- 0.011 to 0.123 +/- 0.012, p < 0.01). In DM hearts, basic MiCS formation was already comparable with that induced by elevated Ca2+ in C hearts and could not be further stimulated by Ca2+. In C, ventricular tachycardia represented 55.4% of the total arrhythmias and occurred in 90% of the animals. In DM rats, the arrhythmia profile was similar to that in C, and the incidence of tachyarrhythmias and their severity were not enhanced (arrhythmia score: 3.18 +/- 0.4 vs. 3.30 +/- 0.3 in C). The infarct size normalized to the size of area at risk was smaller in the DM than in C hearts (52.3 +/- 5.8% vs. 69.2 +/- 2.2%, respectively; p < 0.05). CONCLUSIONS: Ca-signaling represents the link between energy delivery from mitochondria (via MiCS) and energy requirements of the heart. In DM hearts, energy transport via MiCS is elevated to the maximum value. This contributes to increased resistance of DM hearts to irreversible cell damage.

Animals↗
PubMed2002

Preconditioning modulates susceptibility to ischemia-induced arrhythmias in the rat heart: the role of alpha-adrenergic stimulation and K(ATP) channels.

A new concept of cardioprotection based on the exploitation of endogenous mechanisms is known as ischemic preconditioning (IPC). It has been hypothesized that substances released during brief ischemic stress (e.g. catecholamines) stimulate the receptors and trigger multiple cell signaling cascades. Opening of ATP-sensitive K+ channels [K(ATP)] has been suggested as a possible final step in the mechanisms of protection. In this study, the role of adrenergic activation was tested in Langendorff-perfused rat hearts subjected to test ischemia (TI; 30 min occlusion of LAD coronary artery) by: 1) mimicking IPC (5 min ischemia, 10 min reperfusion) with short-term (5 min) administration of norepinephrine (NE, 1 microM), 15 min prior to TI; 2) blockade with beta- or alpha1-receptor antagonists, propranolol (10 microM) and prazosin (2 microM), respectively, applied 15 min prior to TI during IPC. The role of K(ATP) opening was examined by perfusion with a K(ATP) blocker glibenclamide (10 microM) during IPC. Both IPC and NE-induced PC effectively reduced the incidence of ventricular tachycardia (VT) to 33% and 37%, respectively, vs 100% in the non-PC controls, whereby ventricular fibrillation (VF) was totally abolished by IPC and markedly suppressed by PC with NE (0% and 10%, respectively, vs 70% in the non-PC hearts; P < 0.05). The severity of arrhythmias (arrhythmia score, AS) was also markedly attenuated by both interventions (IPC: AS 1.7 +/- 0.4; NE-PC: AS 1.8 +/- 0.3 vs AS 4.1 +/- 0.2 in the controls; P < 0.05). Protection was not suppressed by propranolol (VT 28%; VF 14%; AS 2.2 +/- 0.6), whereas prazosin reversed the protective effect of PC (VT 83%; VF 67%; AS 4.0 +/- 0.8). Antiarrhythmic protection afforded by NE-PC was abolished by pretreatment of rats with pertussis toxin (25 microg/kg, i.p.) given 48 h prior to the experiments. Glibenclamide did not suppress the IPC-induced protection. In conclusion, the sensitivity of the rat heart to ischemic arrhythmias can be modulated by IPC. Protection is mediated via stimulation of alpha1-adrenergic receptors coupled with Gi-proteins but glibenclamide-sensitive K(ATP) channels do not appear to be involved in the mechanisms of antiarrhythmic protection in this model.

Adenosine Triphosphate↗
PubMed2001

Ventricular arrhythmias following coronary artery occlusion in rats: is the diabetic heart less or more sensitive to ischaemia?

Rhythm disorders are common complications in diabetic patients, due to their enhanced sensitivity to ischaemia. However, experimental studies are inconsistent, and both higher and lower vulnerability to injury has been reported. Our objectives were to compare susceptibility to ventricular arrhythmias in rats with prolonged duration of diabetes induced by streptozotocin (45 mg/kg, i.v.), utilising two different models. Following 8 weeks, either anaesthetised open-chest rats in vivo or isolated Langendorff-perfused hearts were subjected to 30 min regional zero-flow ischaemia induced by occlusion of LAD coronary artery. In addition, cardiac glycogenolysis and lactate production were measured. In open-chest rats, 90 % of the controls exhibited ventricular tachycardia (VT) which represented 55.4 % of total arrhythmias, whereby only 19.9 % of arrhythmias occurred as VT in 44 % of the diabetic rats (P < 0.05 vs controls). Duration of VT and ventricular fibrillation (VF) was reduced from 35.5 +/- 11.1 and 224.8 +/- 153.9 s in the controls to 4.8 +/- 2.5 and 2.2 +/- 0.2 s in the diabetics, respectively (P < 0.05). Accordingly, severity of arrhythmias (arrhythmia score, AS) was also lower in the diabetics (2.0 +/- 0.38 vs 3.3 +/- 0.3 in the controls; P < 0.05). In the isolated hearts, high incidence of VF was decreased in the diabetic hearts, and although VT occurred in almost all of the diabetic hearts, the duration of VT and VF was substantially shorter (61.5 +/- 14.5 and 5.5 +/- 0.5 s vs 221.5 +/- 37 and 398.5 +/- 55 s in the controls, respectively; P < 0.05). AS was reduced to 2.9 +/- 0.12 from 4.1 +/- 0.3 in the controls (P < 0.05). Postischaemic accumulation of lactate was lower in the diabetic than in the non-diabetic myocardium (20.4 +/- 1.9 vs 29.5 +/- 2.9 micromol/l/g w.wt.; P < 0.05). These results suggest that rat hearts with chronic diabetes, despite some differences in the arrhythmia profiles between the in vivo model and isolated heart preparation, are less sensitive to ischaemic injury and exhibit lower susceptibility to ventricular arrhythmias and reduced accumulation ofglycolytic metabolites.

Animals↗
PubMed2000

Acute diabetes modulates response to ischemia in isolated rat heart.

Diabetic hearts are suggested to exhibit either increased or lower sensitivity to ischemia. Detrimental effects of prolonged ischemia can be attenuated by preconditioning, however, relatively little is known about its effects in the diseased myocardium. This study was designed to test the susceptibility to ischemia-induced arrhythmias and the effect of preconditioning in the diabetic heart. Rats were made diabetic with streptozotocin (45 mg/kg, i.v.). After 1 week, isolated Langendorff-perfused hearts were subjected to 30 min occlusion of LAD coronary artery without or with preceding preconditioning induced by one cycle of 5 min ischemia and 10 min reperfusion. Glycogen and lactate contents were estimated in the preconditioned and non-preconditioned hearts before and after ischemia. Diabetic hearts were more resistant to ischemia-induced arrhythmias: incidence of ventricular tachycardia (VT) decreased to 42% and only transient ventricular fibrillation (VF) occurred in 17% of the hearts as compared to the non-diabetic controls (VT 100% and VF 70% including sustained VF 36%; p < 0.05). Preconditioning effectively suppressed the incidence and severity of arrhythmias (VT 33%, VF 0%) in the normal hearts. However, this intervention did not confer any additional protection in the diabetic hearts. Despite higher glycogen content in the diabetic myocardium and greater glycogenolysis during ischemia, production of lactate in these hearts was significantly lower than in the controls. Preconditioning caused a substantial decrease in the accumulation of lactate in the normal hearts, whereby in the diabetic hearts, this intervention did not cause any further reduction in the level of lactate. In conclusion, diabetic rat hearts exhibit lower susceptibility to ischemic injury and show no additional response to preconditioning. Reduced production of glycolytic metabolites during ischemia can account for the enhanced resistance of diabetic hearts to ischemia as well as for the lack of further protection by preconditioning.

Animals↗
PubMed2000

Salutary effect of tedisamil on post-ischemic recovery rat heart: involvement of sarcolemmal (Na,K)-ATPase.

The in vitro effect of tedisamil on the specific activity and kinetic parameters of the sarcolemmal (Na,K)-ATPase as well as its ex vivo effect on the (Na,K)-ATPase in the isolated, perfused rat hearts was determined. Five micromol/l of tedisamil was added 5 min before the onset of 30 min global normothermic ischemia followed by 10 min reperfusion. At the conditions of its maximal cardioprotective effect (heart rate reduction, improved postischemic recovery of left ventricular developed pressure), the hearts were immediately used for isolation of sarcolemmal vesicles. In vitro, 1-100 micromol/l of tedisamil produced a concentration-dependent stimulatory effect on (Na,K)-ATPase activity, with a peak seen at 20 micromol/l (p < 0.01), while Mg-dependent ATPase was almost unchanged. Kinetic analysis revealed a significant increase in the affinity of the Na-binding sites on ATPase molecule at 20 micromol/l of tedisamil. These biochemical findings were confirmed by cytochemistry. Moreover, ex vivo experiments revealed that tedisamil rendered the sarcolemmal (Na,K)-ATPase activity to be a more resistant to detrimental effects of ischemia. In conclusion, the cardioprotective action of tedisamil was accompanied with a better preservation of the specific activity of (Na,K)-ATPase.

Animals↗
PubMed2000

Activation of adenylate cyclase system in the preconditioned rat heart.

Ischemic preconditioning (IP) protects the heart against subsequent prolonged ischemia. Whether the beta-adrenoceptor/adenylate cyclase pathway contributes to this cardioprotection is not yet fully known. Using enzyme catalytic cytochemistry we studied the adenylate cyclase activity and its distribution in the preconditioned rat heart. Adenylate cyclase activity was examined in Langendorff-perfused rat hearts subjected to the following conditions: control perfusion; 30 min regional ischemia; 5 min occlusion and 10 min reperfusion (IP); IP followed by ischemia. Ischemia-induced arrhythmias and the effect of ischemic preconditioning on the incidence of arrhythmias were analyzed. At the end of experiment the heart was shortly prefixed with glutaraldehyde. Tissue samples from the left ventricle were incubated in a medium containing the specific substrate AMP-PNP for adenylate cyclase and then routinely processed for electron microscopy. Adenylate cyclase activity was cytochemically demonstrated in the sarcolemma and the junctional sarcoplasmic reticulum (JSR) in control hearts, while it was absent after test ischemia. The highest activity of the precipitate was observed after ischemic preconditioning. In the preconditioned hearts followed by test ischemia, adenylate cyclase activity in the precipitate was preserved in sarcolemma and even more in JSR. Protective effect of ischemic preconditioning was manifested by the suppression of severe arrhythmias. These results indicate the involvement of the adenylate cyclase system in mechanisms underlying ischemic preconditioning.

Adenylyl Cyclases↗
PubMed2000

Susceptibility to ischemia-induced arrhythmias and the effect of preconditioning in the diabetic rat heart.

Diabetic heart is suggested to exhibit either increased or decreased resistance to ischemic injury. Ischemic preconditioning suppresses arrhythmias in the normal heart, whereas relatively little is known about its effects in the diseased myocardium. Our objective was to investigate whether development of diabetes mellitus modifies the susceptibility to ischemia-induced arrhythmias and affects preconditioning in the rat heart. Following 1 and 9 weeks of streptozotocin-induced (45 mg/kg, i.v.) diabetes, the hearts were Langendorff-perfused at constant pressure of 70 mm Hg and subjected to test ischemia induced by 30 min occlusion of the left anterior descending (LAD) coronary artery. Preconditioning consisted of one cycle of 5 min ischemia and 10 min reperfusion, prior to test ischemia. Susceptibility to ischemia-induced arrhythmias was lower in 1-week diabetics: only 42 % of diabetic hearts exhibited ventricular tachycardia (VT) and 16 % had short episodes of ventricular fibrillation (VF) as compared to VT 100 % and VF 70 % (including sustained VF 36 %) in the non-diabetics (P<0.05). Development of the disease was associated with an increased incidence of VT (VT 92 %, not significantly different from non-diabetics) and longer total duration of VT and VF at 9-weeks, as compared to 1-week diabetics. Preconditioning effectively suppressed arrhythmias in the normal hearts (VT 33 %, VF 0 %). However, it did not provide any additional antiarrhythmic protection in the acute diabetes. On the other hand, in the preconditioned 9-weeks diabetic hearts, the incidence of arrhythmias tended to decrease (VT 50 %, transient VF 10 %) and their severity was reduced. Diabetic rat hearts are thus less susceptible to ischemia-induced arrhythmias in the acute phase of the disease. Development of diabetes attenuates increased ischemic tolerance, however, diabetic hearts in the chronic phase can benefit more from ischemic preconditioning, due to its persisting influence.

Animals↗
PubMed2000

Postischemic reperfusion of the spinal cord: prolonged reperfusion alleviates the metabolic alterations induced by 25 min ischemia in the cervical and thoracolumbal segments.

In recent years, increasing amount of information has indicated that in some tissues the main damage due to oxidative stress does not occur during reperfusion but during the ischemic episode of the ischemia/reperfusion event. In this respect, serious doubts were also expressed about the origin of the increased amounts of free radicals which were believed to form and reported to appear in the perfusate during the first minutes of reperfusion. Moreover, speculative explanations were only available for a second increase in lipid peroxidation which was reported to occur after postischemic reperfusions exceeding 60 min. For this reasons, the present paper reports the results of investigation of ischemia/reperfusion injury to the cervical (CE) and thoracolumbal (ThL) segments of the spinal cord (SP) after an acute 25 min occlusion of the abdominal aorta, followed by 60-120 min reperfusion of the ischemic areas in rabbits. In CE and ThL segments of the SP, the ischemia induced: 1) a decrease in activities of superoxide dismutase (SOD), from 57.35+/-6.36 to 45.27+/-5.45 U x mg(-1) x min(-1) (S.E.M., 20.92%), p < 0.01, and from 58.36+/-5.45 to 33.00+/-4.55 U x mg(-1) x min(-1) (S.E.M., 43.46%), p < 0.001; 2) a significant decrease in gamma-glutamyl transpeptidase (gamma-GTP), from 114.66+/-1.45 to 99.88+/-4.4 micromol p-nitroaniline x mg(-1) x h(-1) (S.E.M. 12.89 %), p < 0.05 and from 112.24+/-1.20 to 95.09+/-2.40 micromol p-nitroaniline x mg(-1) x h(-1) (S.E.M., 16.26%), p < 0.05; 3) a considerable depression in Na,K-ATPase activity, from 7.14+/-0.58 to 5.08+/-0.32 micromol Pi x mg(-1) x h(-1) (S.E.M., 28.86%), p < 0.01, and from 7.23+/-0.11 to 5.09+/-0.31 micromol Pi x mg(-1) x h(-1) (S.E.M., 30.00%), p < 0.01. The Na,K-ATPase activity became decreased by ischemia and remained depressed significantly (all p < 0.01) throughout the experiment. After 60 min of reperfusion, SOD activity in the CE segment and that of gamma-GTP in the CE as well as ThL segments recovered, even slightly surpassing the control values, wheras SOD activity in the ThL segment became stabilized again close to its post-ischemic value. Prolonged, reperfusion for 120 min resulted in a further increase in gamma-GTP activity in the CE and ThL segments (to 132.79 and 132.30%, p < 0.01), and this was accompanied by a slight (p > 0.05) elevation in the content of conjugated dienes as well as by a new wave of depression of the SOD activity (p < 0.05) in both the CE and the ThL segment. From our results it could be concluded that all considerable damage to the spinal cord occurred during the ischemic period. In the period of reperfusion reparative changes started to predominate. This is in accordance with the recent discoveries indicating that, when coupled with an increase in tissue gamma-GTP activity, the post-ischemic reparative changes comprise a replenishment of the cell glutathione pool. This process is accompanied with a gradual increase in H2O2 production that results in repeatead inhibition of the SOD activity and a tendency to conjugated dienes formation.

Animals↗
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↗