Biomedical subjects

L Szekeres

Publications and source records attributed to L Szekeres.

At least 19 recordsLinked to original sources

PubMed1995

Delayed protection of the heart against ischaemia.

Ischaemic preconditioning is the protective adaptive mechanism produced by short periods of ischaemic stress that results in a marked resistance of the myocardium to prolonged periods of the same stress; however, this protection is transient. There is now evidence that protection resulting from preconditioning returns several hours later, and here James Parratt and Laszlo Szekeres highlight the possible importance of this concept, which may lead to novel approaches to the long-term protection of the heart against ischaemic injury.

Animals↗

PubMed1995

Left ventricular dysfunction induced by occlusion of coronary arteries in conscious dogs.

The aim of the present study was to investigate stable left ventricular dysfunction resulting from severe myocardial ischemia in conscious dogs, in order to evaluate the action of cardiotonic agents under pathological conditions mimicking moderate cardiac failure. Mongrel dogs with a catheter implanted in the left ventricle were trained on a treadmill and subjected to a standardized exercise before and after a Harris-type ligation of the anterior descending branch of the left coronary artery in two stages. Two weeks later the lower third of the left circumflex coronary branch was also occluded, and the exercise test repeated for at least two additional weeks to evaluate the changes in the left ventricular function indicated by left ventricular systolic pressure, end-diastolic pressure, heart rate, positive and negative dP/dtmax and dP/dt/P. Noninvasive radionuclide investigations of the left ventricular function and myocardial perfusion were done before and after the development of cardiac failure. Following occlusion of the anterior descending and circumflex coronary arteries, the baseline end-diastolic pressure increased from 7.6 +/- 2.3 mmHg to 23.3 +/- 3.0 mmHg (p < 0.05) and increased even further during exercise (to 49.2 +/- 3.5 mmHg, p < 0.05). After the development of cardiac failure, no substantial change occurred in the end-diastolic pressure, either during rest or repeated exercise tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Long lasting anti-adrenergic effect of 7-oxo-prostacyclin in the heart: a cycloheximide sensitive increase of phosphodiesterase isoform I and IV activities.

Evidence is accumulating that 7-oxo-prostacyclin (7-oxo-PGI2) induces a delayed indirect anti-adrenergic and cytoprotective effect on the myocardium, the mechanism of which is still unclear. To demonstrate that a single application of 7-oxo-PGI2 (50 micrograms/kg i.m.) 48 h prior to starting experiments attenuates the isoprenaline inducible inotropic response and accumulation of cAMP, isolated hearts of pretreated animals were perfused in the Langendorff mode with and without isoprenaline (1 to 100 nM). The late anti-adrenergic effect of the drug was manifested by a significant attenuation in the elevation of cAMP levels as well as in contractile force development. This effect was not due to changes in cAMP generation as there were identical beta 1-adrenoceptor densities and affinities (as calculated from [3H]-CGP binding studies), Gi and G alpha s protein patterns (as taken from Western blots) as well as adenylyl cyclase activity measurements in the hearts studied. The anti-adrenergic potency of 7-oxo-PGI2, however, was found to be related to a significant rise in cyclic nucleotide hydrolysis by phosphodiesterase (PDE). Using the fast-performance liquid chromatographic separation for PDE isoforms, a significant increase in the activity of PDE isoforms I and IV (260 +/- 28 vs 110 +/- 12 pmol cGMP/min x enzyme fraction and 77 +/- 11 vs 34 +/- 3 pmol cAMP/min x enzyme fraction, respectively) was found in the solubilized fraction of cardiac membranes in comparison to untreated controls; PDE IV activity was also increased in the cytosolic fraction (106 +/- 14 vs 65 +/- 6 pmol cAMP/min x enzyme fraction). The hypothesis that the delayed anti-adrenergic effect of 7-oxo-PGI2 is initiated by an induction and accelerated synthesis of PDE I and IV in the heart is underlined by the fact that cycloheximide suppresses completely both the rise in PDE activities and the anti-adrenergic effects studied. It is suggested that an inducible predominance of cAMP degradation over its generation may be of relevance in processes related to heart protection.

Adenylyl Cyclases↗

PubMed1993

[Reliability of clinical diagnosis in malignant melanoma].

During the last 10 years (1981-1990) 14,178 skin tumors were histologically examined in the Department of Dermatology of the University Medical School of Szeged. Of these lesions 520 were diagnosed clinically and histologically as malignant melanoma (true-positive). 104 lesions were clinically diagnosed as malignant melanoma but were found histologically to be other tumors (false-positive). An additional 78 cases diagnosed clinically as other than malignant melanomas, were found histologically to be malignant melanoma (false-negative). The clinical diagnostic accuracy was 74.07%. The index of suspicion was 104.34%, thus demonstrating a slight degree of "overdiagnosis". The sensitivity, specificity and predictive values were consonant with those of the literature.

Basal Cell Carcinoma↗

PubMed1993

Release of 6-keto-PGF1 alpha and thromboxane B2 in late appearing cardioprotection induced by the stable PGI analogue: 7-OXO-PGI.

We have shown earlier that prostacyclin (PGI2) and its stable analogue: 7-oxo-prostacyclin(7-OXO) may induce a prolonged, late appearing (24-48 h after drug administration), dose dependent protection of the heart from harmful consequences of a subsequent severe ischaemic stress, such as myocardial ischaemia, life-threatening ventricular arrhythmias and early ischaemic morphological changes. In an other study we observed that a similar but shortlived (less than 1 h) cardioprotection, induced by 'preconditioning' brief coronary artery occlusions, is greatly reduced by blockade of the cyclooxygenase pathway, suggesting that prostanoids might play a role in this shortlasting protection. Objective of our present study was to elucidate the importance of some arachidonic acid (AA) metabolites, such as PGI2 and thromboxane A2 (TXA2) in the mechanism of the late appearing, prolonged cardioprotection. Estimation of the metabolites: 6-keto-PGF1 alpha (6-KETO) and thromboxane B2 (TXB2) was made from the perfusate of isolated Langendorff hearts of guinea-pigs pretreated with 50 micrograms/kg 7-OXO, 24 and 48 h before preparation. Pretreatment alone produced a slight, but significant elevation of 6-KETO (from 206 +/- 11 to 284 +/- 19 pg/ml/min after 24 h, and to 261 +/- 18 pg/ml/min after 48 h). No change was seen in TXB2 production. Global ischaemia for 25 min (followed by 25 min reperfusion) markedly increased the release of both AA metabolites; maximal values were observed in the third min of reperfusion (6-KETO from 206 +/- 11 to 1275 +/- 55 pg/ml/min and TXB2 from 29 +/- 4 to 172 +/- 12 pg/ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

PubMed1993

Moderate stress by cardiac pacing may induce both short term and long term cardioprotection.

OBJECTIVE: The aim was to investigate whether moderate ischaemic stress induced by brief periods of cardiac pacing to twice the normal heart rate protects the heart from the electrophysiological and haemodynamic consequences of subsequent periods of rapid pacing. METHODS: Conscious rabbits with implanted right ventricular electrodes and a permanent catheter in the left ventricular cavity were studied. Hearts were paced at a rate of 500.min-1 for 5 min. The resulting transient ST segment elevation in intracavital electrogram, the ventricular effective refractory period, and the left ventricular end diastolic pressure were measured. RESULTS: After discontinuation of pacing, a shortlasting ST segment elevation appeared in the endocardial electrogram, together with a transient rise in left ventricular end diastolic pressure. These changes were significantly reduced after a second pacing, provided that this was applied not later than 30 min after the first pacing; maximum protection occurred when there was a 5 min interval between these pacing periods. Serial stimulation (10 pacing periods with a 5 min interval between each) gave a similar protection to that resulting from a single pacing period. The protection was lost after 1 h; however, 24 h and 48 h (but not 72 h) after the end of serial stimulation there was again a reduction in postpacing ST segment and left ventricular end diastolic pressure elevation. At these times the ventricular effective refractory period was prolonged. The cyclo-oxygenase inhibitor sodium meclofenamate (1-2 mg.kg-1) prevented the early protection. CONCLUSIONS: The results suggest that brief periods of rapid pacing induce both short term and long term cardioprotection, as shown by reduced electrophysiological and haemodynamic consequences of subsequent pacing periods. Endogenous prostanoids might play a role in the short term cardioprotection.

Animals↗

PubMed1993

Are ATP sensitive potassium channels involved in the pronounced antiarrhythmic effects of preconditioning?

OBJECTIVE: The aim was to determine whether the antiarrhythmic effects of preconditioning are modified by blockade of K+ATP channels with glibenclamide in a model (anaesthetised dogs) in which this procedure has previously been shown to prevent the effects of preconditioning in reducing myocardial infarct size. METHODS: 10 mongrel dogs were preconditioned by two 5 min occlusions of the left anterior descending coronary artery, separated by a 20 min reperfusion period, and then subjected, 20 min later, to a prolonged (25 min) occlusion and to subsequent reperfusion. In another 10 dogs glibenclamide (300 micrograms.kg-1) was given by intravenous injection both after the first preconditioning stimulus and before the prolonged occlusion. Control dogs (25) were subjected to a 25 min occlusion followed by reperfusion; five of these dogs also received glibenclamide. RESULTS: Preconditioning reduced the severity of ventricular arrhythmias, epicardial ST segment elevation, and the degree of inhomogeneity of conduction. The antiarrhythmic effect of preconditioning was attenuated by glibenclamide (twice as many ventricular premature beats and more episodes of ventricular tachycardia) but there was no modification of preconditioning induced reduction in ventricular fibrillation either during ischaemia or during reperfusion, or on survival (0% in controls; 50% in preconditioned dogs with or without glibenclamide). Glibenclamide did, however, prevent the effects of preconditioning on the inhomogeneity of conduction and, less markedly, on epicardial ST segment elevation. CONCLUSIONS: In a similar model to that in which it has previously been shown that glibenclamide prevents the effect of preconditioning in reducing myocardial infarct size (suggesting involvement of K+ATP channels), the most pronounced antiarrhythmic effects of preconditioning (reduction in ventricular fibrillation; increase in survival) were not modified by glibenclamide. This, and other evidence, suggests that the mechanisms of the protective effect of preconditioning in reducing the severity of arrhythmias and on infarct size are not the same.

Adenosine Triphosphate↗

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

Prevention by an inhibitor of the L-arginine-nitric oxide pathway of the antiarrhythmic effects of bradykinin in anaesthetized dogs.

The intracoronary administration of bradykinin (25 ng kg-1 min-1) markedly reduces the severity of arrhythmias that occur during a 25 min occlusion of the left anterior descending coronary artery in chloralose, urethane anaesthetized dogs. This protection was abolished by the prior administration, by the same route, of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of the L-arginine-nitric oxide pathway. The protective effect of bradykinin on reperfusion-induced VF was not affected by L-NAME. These results strongly suggest that the antiarrhythmic effect of bradykinin in this model is mediated by nitric oxide release. It also supports the concept that bradykinin might be a 'primary mediator' of the protective, antiarrhythmic effects of ischemic preconditioning.

Anesthesia↗

PubMed1992

Antiarrhythmic effects of preconditioning in anaesthetised dogs and rats.

OBJECTIVE: The aim was to determine the relationship of the duration of short coronary artery occlusions and of the reperfusion period to the extent of the antiarrhythmic effect of preconditioning. METHODS: A prolonged occlusion of a coronary artery in 102 anaesthetised rats and 55 anaesthetised dogs was preceded by a variable number of preconditioning coronary artery occlusions, of varying duration and with variable reperfusion periods between them and the prolonged occlusion. RESULTS: Preconditioning in both species reduced the severity of ischaemia induced arrhythmias, epicardial ST segment changes, and alterations in the degree of inhomogeneity of conduction during a subsequent prolonged coronary artery occlusion, provided that the reperfusion time was less than 30 min (in rats) and 1 h (in dogs). This antiarrhythmic effect of preconditioning was marked; eg, in dogs following two preconditioning occlusions survival from a combined ischaemia-reperfusion insult was 40% (cf, 0% in the controls). CONCLUSIONS: Short preconditioning periods of myocardial ischaemia protect the myocardium against the arrhythmogenic effects of a more prolonged occlusion. The optimum time for this preconditioning occlusion in rats is 3 min and protection is still apparent 30 min later. In dogs, the protective effect is especially clear with two short (5 min) coronary artery occlusions. The protection in this species lasts for less than 1 h.

Animals↗

PubMed1992

Effect of dietary sunflower seed oil on the severity of reperfusion-induced arrhythmias in anesthetized rats.

Myocardial ischemia followed by reperfusion was produced in artificially respirated, open-chest rats. Coronary artery ligation for 6 min rarely evoked arrhythmias; however, reperfusion after this period rapidly produced severe dysrhythmias in all control animals. Reperfusion after 12 min of ischemia produced less frequent dysrhythmias than after coronary occlusion for 6 min. Feeding of a linoleic acid-rich diet, applying 12% sunflower seed oil in rat food pellet for 4 weeks, decreased the incidence of reperfusion-induced ventricular fibrillation both after 6 min (2/15 vs. 7/11) and 12 min (0/11 vs. 2/8) of myocardial ischemia and the incidence of other arrhythmias was also decreased. The number of animals developing no arrhythmias during reperfusion was increased (8/15 after 6 min of ischemia, 4/11 after 12 min of ischemia vs. 0/11 and 0/8 in controls, respectively). Our results indicate that increased dietary consumption of linoleic acid decreased the occurrence of life-threatening arrhythmias both during the acute phase of myocardial ischemia and during reperfusion in anesthetized rats.

Anesthesia↗

PubMed1992

The local intracoronary administration of methylene blue prevents the pronounced antiarrhythmic effect of ischaemic preconditioning.

Short periods of coronary artery occlusion (2 x 5 min) markedly reduce the severity of arrhythmias and the changes in ST-segment elevation and in the degree of inhomogeneity of conduction during a subsequent 25 min occlusion of the left anterior descending coronary artery in anaesthetized dogs. These changes were completely reversed if methylene blue (5 mg min-1) was infused into a side branch of the coronary artery throughout both the preconditioning and prolonged occlusions. These results suggest that the pronounced antiarrhythmic effects of preconditioning result from activation of guanylyl cyclase and result in increased levels of guanosine 3':5'-cyclic monophosphate.

Animals↗

PubMed1992

Preconditioning of the ischaemic myocardium; involvement of the L-arginine nitric oxide pathway.

1. Short periods of coronary artery occlusion protect the heart against the effects of a subsequent prolonged period of ischaemia. This phenomenon is known as preconditioning of the ischaemic myocardium. 2. In mongrel, chloralose-urethane anaesthetized open-chest dogs, within a restricted body weight range, two 5 min periods of occlusion of the anterior descending branch of the left coronary artery markedly reduced the severity of the early ischaemic arrhythmias resulting from a prolonged (25 min) occlusion of the same coronary artery starting 20 min later. Thus, the number of ventricular premature beats (VPBs) was reduced from 528 +/- 140 in controls to 78 +/- 27 in preconditioned dogs, the incidence of ventricular fibrillation (VF) was reduced from 47% to 0% and the incidence of ventricular tachycardia (VT) from 100% to 20%. ST-segment elevation recorded from electrodes within the ischaemic area, and the degree of inhomogeneity of conduction within the ischaemic area were markedly reduced in these preconditioned dogs. 3. The incidence of VF following reperfusion of the ischaemic myocardium at the end of the 25 min occlusion period was reduced in the preconditioned dogs from 100% to 60%; there was thus a 40% survival from the combined ischaemia-reperfusion insult compared with 0% in the controls. 4. NG-nitro-L-arginine methyl ester (L-NAME) an inhibitor of the L-arginine nitric oxide pathway, given in a dose of 10 mg kg-1 intravenously on two occasions, both before the initial preconditioning occlusion and then again before the prolonged occlusion, partially attenuated the protective effects of preconditioning.There were more VPBs (220 +/- 75), a higher incidence of VT (60%) and more episodes of VT (11.5 +/- 6.0 compared to 0.7 +/- 0.3 episodes in the preconditioned dogs not given L-NAME); none of the animals survived reperfusion (incidence of VF 100%). The improvement in the severity of the degree of in homogeneity which resulted from preconditioning was abolished by L-NAME administration.5. L-NAME itself elevated blood pressure (from 96 +/- 5 mmHg diastolic to 119 +/- 7 mmHg), reduced heart rate (from 155 +/- 7 to 144 +/- 4 beats min-') but did not change LVEDP, LVdP/dt,,,,, coronary blood flow, ST-segment elevation or the degree of inhomogeneity of conduction. When given 10 min before the prolonged coronary artery occlusion in dogs not subjected to preconditioning, L-NAME had no significant effect on the severity of arrhythmias except for more periods of VT (a mean of 11.7 +/- 4.7episodes per dog).6. It is concluded from these studies that the generation of nitric oxide contributes to the marked antiarrhythmic effects of preconditioning in the canine myocardium, probably through elevation of cyclic GMP.

Animals↗

PubMed1992

Electrophysiological changes induced by lysophosphatidylcholine, an ischaemic phospholipid catabolite, in rabbit atrial and ventricular cardiac cells.

The effects of palmitoyl-lysophosphatidylcholine (LPC) were studied on the cellular electrical activity of rabbit heart preparations. LPC (100 mumol/l) caused a considerable enhancement of the automaticity of the SA nodal and Purkinje fibers and frequently induced irregular firing in both supraventricular (SA node, atrium, AV junction) and ventricular (Purkinje fibers, papillary muscle) myocardial regions. The 'automatotropic' and arrhythmogenic effects of LPC were accompanied by a lengthening of the atrioventricular conduction time. In ventricular muscle fibers LPC (100 mumol/l) decreased the resting potential (RP), the maximum rate of depolarization (Vmax) and the amplitude (APA) and duration (APD) of the action potential, and often evoked action potentials of 'slow response' type. In atrial muscle cells, 100 mumol/l LPC was capable of inducing hyperpolarization, with concomitant increases in RP, Vmax, APA and APD; higher concentrations (300 and 600 mumol/l) of LPC resulted in decreases in RP, Vmax, APA and APD, i.e. phenomena similar to those observed with 100 mumol/l LPC in the ventricular myocardium. The results seem to support the assumption that lysolipids accumulating in the ischaemic myocardium may play a pathogenetic role in the development of both supraventricular and ventricular dysrhythmias accompanying coronary artery occlusion.

Animals↗

PubMed1991

[Family studies on the incidence of multiple pigmented naevi, familial skin melanoma and other malignant tumors].

102 family members of 14 patients with primary melanoma and multiple atypical pigmented naevi were investigated. Additionally to 14 patients with melanoma, 31 family members were found to have multiple atypical pigmented naevi. Most of them had light complexion and poor pigmentation capacity. A relative high frequency of malignant tumors other than melanoma were observed among blood relatives without multiple naevi. Members of melanoma-prone families need regular medical surveillance.

Adult↗

PubMed1991

Effect of cicletanine on overpacing-induced ST-segment elevation in conscious rabbits. A comparison with verapamil.

We compared the effects of cicletanine (10 mg/kg i.v.) and verapamil (0.1 mg/kg i.v.) on heart rate, ventricular effective refractory period, systolic and diastolic arterial blood pressure and overpacing-induced ST-segment elevation detected by right ventricular intracavital electrogram in conscious rabbits. Cicletanine significantly reduced overpacing-induced ST-segment elevation, which is an indicator of myocardial ischemia, and heart rate, but did not influence blood pressure and ventricular effective refractory period. Verapamil did not significantly influence ventricular effective refractory period, blood pressure or heart rate, but reduced the ST-segment elevation induced by frequency loading. These results suggest that acute treatment with cicletanine induces an anti-ischemic effect in the overpaced heart of conscious rabbits.

Animals↗

PubMed1991

Cardioprotection: endogenous protective mechanisms promoted by prostacyclin.

Evidence is accumulating that acute stress situations such as ischemia, adrenergic dominance, and ouabain intoxication enhance production of endogenous substances (PgI2, adenosine, NO) which may protect the myocardium from harmful consequences of these stress situations. PgI2 and its stable analogue 7-oxo-PgI2 exert an early direct- and induce a delayed indirect antiischemic, antiarrhythmic, and cytoprotective effect. The direct action is shortlasting; it protects from myocardial ischemia and arrhythmias, at least partly, by its vasodilating, antiaggregatory, and "membrane-stabilizing" effects. The delayed, long-lasting PgI2-induced protection from postocclusion, reperfusion- and ouabain-arrhythmias is dose- (optimal 50 micrograms/kg) and time- (optimal 48 h after treatment) dependent. Its mechanism is probably based on a 7-oxo-PgI2 induced increase in the activity of Na/K-ATP-ase, and further, on a reduced sensitivity to beta-adrenergic agonists and to changes at the cardiac membrane level, resulting in a prolongation of the action potential duration and the effective refractory period.

Animals↗

PubMed1991

Transient ischaemia induced by rapid cardiac pacing results in myocardial preconditioning.

STUDY OBJECTIVE: The aim was to determine whether rapid ventricular pacing can protect against the ventricular arrhythmias occurring during a subsequent coronary artery occlusion. DESIGN: The effect was examined of two 2 min periods of pacing (300 beats.min-1) in chloralose-urethane anaesthetised dogs on a subsequent 25 min coronary artery occlusion. Ventricular arrhythmias, ST segment elevation, and inhomogeneity of conduction were analysed. EXPERIMENTAL MATERIAL: 25 anaesthetised mongrel dogs in a restricted body weight range were used. MEASUREMENTS AND MAIN RESULTS: Preocclusion pacing reduced the severity of occlusion induced ST segment elevation, degree of inhomogeneity, and arrhythmias: ventricular premature beats were reduced from 528(SEM 40) to 136(45), and there were lower incidences of ventricular fibrillation (0% v 47%) and ventricular tachycardia (30% v 80%). CONCLUSIONS: Rapid ventricular pacing "preconditions" the myocardium in a manner similar to that following short coronary artery occlusions. Short periods of ischaemia no matter how induced protect the heart against the arrhythmogenic effect of a prolonged coronary artery occlusion.

Animals↗