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Biomedical subjects

L Szekeres

Publications and source records attributed to L Szekeres.

At least 73 records · Page 4Linked to original sources
PubMed1987

Verapamil in a new model of severe local myocardial ischaemia due to combined coronary occlusion and stenosis.

The effect of verapamil was studied in a new canine model of local myocardial ischaemia. In this model in addition to the critical construction of the left circumflex coronary artery, the left anterior descending branch was suddenly occluded. Experiments were performed in the anaesthetized, thoracotomized and artificially respired dog. The model represents a severe form of myocardial ischaemia and mimics the clinical situation in which usually more than one coronary artery is involved in the stenotic process. Verapamil (0.15 mg kg -1 i.v.) moderated the extent of the ischaemic changes (indicated by the ST segment elevation in the epicardial and endocardial ECG) as well as their consequences e.g. the incidence and severity of early postocclusion and reperfusion arrhythmias. This beneficial effect was probably due to the drug-induced favourable haemodynamic action (reduction of left ventricular end-diastolic pressure and slight increase in left ventricular dP/dtmax) and to the electrophysiological effects (e.g. decreased inhomogeneity of electrical activation, diminution of extrasystolic activity) and blood flow changes (enhanced blood supply to the ischaemic subepicardium).

Animals↗
PubMed1987

Glucocorticoid-induced low molecular mass anti-inflammatory factors which do not inhibit phospholipase A2.

The peritoneal lavage fluid of dexamethasone (DXM)-pretreated rats was filtered through an Amicon YM-10 membrane (cutsize 10 kD). The retentate inhibited dextran oedema. Its 40 kD fraction (lipocortin) obtained by molecular sieving on Sephadex (SG)-75, suppressed carrageenin-induced foot swelling and phospholipase A2 (PLA2) activity, but it had no effect on the dextran response. The Amicon filtrate was chromatographed on SG-25 gel and yielded 6 and 2 kD fractions suppressing dextran and serotonin (5-HT) oedema but not carrageenin inflammation and PLA2 activity. These fractions may be active fragments of vasocortin, a glucocorticoid-induced mediator regulating vascular permeability.

Adrenalectomy↗
PubMed1987

Cardioprotection by anti-ischaemic and cytoprotective drugs.

Cardioprotective drugs are agents that prevent or moderate harmful consequences of impaired cardiac energetics, such as sudden coronary death (SCD) due to early post-occlusion ventricular fibrillation (EPVF), development of incapacitating myocardial necrosis. Cardioprotection may be due to anti-ischaemic action, correcting the imbalance between vascular supply and myocardial demand for blood, but also to cytoprotective effect, preserving cellular integrity in the presence of factors damaging structure and function of the cardiac cell membrane such as ischaemia, ionic imbalance and that of pH, etc. Neither anti-ischaemic nor cytoprotective effect alone, or in combination, are sufficient to warrant full cardioprotection, i.e. both prevention of SCD and limitation of infarct size. Thus the beta-blocker pindolol which is anti-ischaemic in its effect reducing myocardial O2 demand and protects from SCD and EVFP, failed to limit infarct size. Even interventions of a mainly cytoprotective type of action protecting from SCD and EPVF, such as the linoleic acid-rich diet, or lidocaine, were unable to limit infarct size, 7-oxoPGI2 (anti-ischaemic and cytoprotective) failed to protect from SCD, VF and did not limit infarct size. On the other hand the nonsteroidal anti-inflammatory drugs which, like salicylates or sulfinpyrazon, reduce myocardial O2 demand and protect from post-occlusion SCD and EPVF, effectively limiting infarct size.

Animals↗
PubMed1987

Diltiazem and the reduction of reperfusion-induced arrhythmias in the rat: protection is secondary to modification of ischemic injury and heart rate.

We have used the isolated rat heart with transient coronary artery occlusion to investigate whether diltiazem has an anti-arrhythmic action against reperfusion-induced ventricular arrhythmias. In the first series of studies (early administration group) the drug was administered 5 min prior to the induction of regional ischemia, this resulted in a dose-dependent reduction in reperfusion-induced ventricular fibrillation. With 5 X 10(-8), 10(-7), 5 X 10(-7), 10(-6) and 5 X 10(-6) mols of diltiazem/l, total ventricular fibrillation (reversible plus irreversible) was reduced from its control incidence of 100% (12/12) to 91%, 58% (P = less than 0.05), 17% (P = less than 0.001), 0% (P = less than 0.001) and 0% (P = less than 0.001) respectively. Heart rate was also reduced in a dose-dependent manner, falling from its control value of 268 +/- 6 beats/min to less than 50% with the highest concentration of diltiazem. Coronary flow was increased in a dose-dependent manner in the diltiazem treated groups. In additional studies with an anti-arrhythmic dose of diltiazem (5 X 10(-7) mols/l), hearts were paced to their drug free control value; under these conditions the anti-arrhythmic effect of diltiazem was lost. In further studies, diltiazem (10(-7) and 5 X 10(-7) mols/l) was administered just prior to reperfusion (late administration group), no anti-arrhythmic effects were observed. In additional studies we determined whether, with early administration, diltiazem (5 X 10(-7) mols/l) exerted its anti-arrhythmic effect by altering the relationship between the vulnerability to reperfusion-induced arrhythmias and the duration of preceding ischemia. In diltiazem-free control hearts a bell-shaped profile was observed with a maximum vulnerability after 10 min of ischemia (100% incidence of reperfusion-induced ventricular fibrillation). In diltiazem-treated hearts, a bell-shaped curve was also observed, however, its optimum was shifted to the right and downwards (20 min of ischemia gave maximum vulnerability [41%] to reperfusion-induced arrhythmias). We conclude that the ability of diltiazem to protect the isolated rat heart against reperfusion-induced arrhythmias is secondary to its anti-ischemic effect and in particular to its negative chronotropic properties.

Animals↗
PubMed1987

Metoprolol reduces reperfusion-induced fibrillation in the isolated rat heart: protection is secondary to bradycardia.

We studied the effect of metoprolol on the incidence of reperfusion-induced ventricular fibrillation in the isolated rat heart with transient coronary artery occlusion and reperfusion. When administered prior to ischemia, metoprolol produced a dose-dependent reduction in reperfusion-induced ventricular fibrillation. Thus, with 1, 10, 30, 50, 100, and 200 mumol/L metoprolol, total ventricular fibrillation (reversible plus irreversible) was reduced from its control incidence of 100% to 91%, 83%, 58% (p less than 0.05), 25% (p less than 0.001), 25% (p less than 0.001), and 0% (p less than 0.001), respectively. Heart rate was also reduced in a dose-dependent manner from its control value of 268 +/- 6 beats/min to less than 75% at the highest concentration of metoprolol. Coronary flow was unaffected by metoprolol. Doses of metoprolol (1 and 10 mumol/L) that had no significant effect on heart rate had no antiarrhythmic effect. In additional experiments with a higher dose of metoprolol (50 mumol/L), hearts were paced to the rate of the drug-free control group and the antiarrhythmic effect of metoprolol was lost. When drug-free control hearts had their heart rate reduced to that of the metoprolol-treated hearts, a similar antiarrhythmic effect was observed. When metoprolol was administered just prior to reperfusion, no antiarrhythmic effects were observed. In further studies, we investigated the effect of the early administration of metoprolol (50 mumol/L) on the relationship between the vulnerability to reperfusion-induced arrhythmias and the duration of preceding ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Nifedipine effects in severe myocardial ischaemia in the dog due to left anterior descending coronary occlusion with left circumflex coronary artery constriction.

The effects of nifedipine were studied in a model of local myocardial ischaemia, comprising anaesthetized thoracotomized dogs in which a critical constriction of the left circumflex coronary artery (LCX) was combined with sudden occlusion of the left anterior descending coronary artery (LAD). Since more than one coronary artery is involved in ischaemic heart disease, the model seems to reflect the clinical situation very closely. In this model, infusion of 1 microgram kg-1 min-1 nifedipine increased myocardial blood flow within the stenosed area served by the LCX as well as in the myocardial region supplied by the LAD, mainly in the subepicardium. Accordingly, the drug reduced ischaemic ST-segment elevation only in the epicardium. It is suggested that nifedipine directed flow to the sub-epicardium of the ischaemic area by improving the collateral circulation. This redistribution of flow resulted in a decrease in the endo/epicardial flow ratio. Nifedipine did not change the inhomogeneity of electrical activation indicating that it has no effect on the ischaemia-induced conduction delay. At the same time nifedipine was not able to reduce either the number of extrasystoles appearing in the early postocclusion and reperfusion phase or the incidence of ventricular fibrillation occurring mainly during reperfusion.

Animals↗
PubMed1987

Comparison of some haemodynamic parameters determined by invasive methods as well as by the noninvasive radionuclide estimation of the left ventricular ejection fraction in conscious and anaesthetized dogs.

An attempt was made to elaborate an optimal method for noninvasive radionuclide determination of left ventricular ejection fraction in conscious and lightly anaesthetized dogs, as well as to assess the value of this procedure in estimating cardiac functional state. Repeated determinations in the same animals have shown that the 45 degree left anterior oblique position (LAO-45) for imaging is optimal, giving the most uniform values of the calculated left ventricular ejection fraction. Neither the latter, nor the haemodynamic parameters (LVSP, LVEDP and dP/dt) determined by invasive methods were changed by light pentobarbital anaesthesia (20 mg/kg i. v.). Results confirm the validity of noninvasive radionuclide determination of left ventricular ejection fraction for estimation of the functional state and of the pharmacological actions on the latter in both conscious and anaesthetized animals.

Angiocardiography↗
PubMed1987

Ion shifts in myocardial cells during ischemia and reperfusion and the effect of membrane stabilizing agents on ischemic ion transport.

Ischemia-and reperfusion-induced time dependent changes of the intracellular K+/K+i/, Na+/Na+i/ and Ca2+/Ca2+i/ concentrations were analyzed in isolated Langendorff guinea pig hearts. In the ischemic period evoked by complete perfusion stop of 25 min duration a rapid loss of K+ and gain of Na+ was found. Ca2+i concentration started to increase only after 15 min of global ischemia. Reperfusion did not evoke substantial changes during the first minutes however Ca2+i very rapidly increased after 7 minutes of reperfusion. K+i rapidly increased above initial values in the first 3 minutes of reperfusion but then suddenly declined to the lowest ischemic level and remained at this level. Na+i concentration elevated by ischemia was not further affected by reperfusion. The membrane stabilizing antiarrhythmic agents: quinidine and lidocaine proved to be effective in preventing or moderating ischemia induced shifts in K+i and Na+i concentrations however did not affect Ca2+i content. This latter was markedly reduced by verapamil, a substance which failed to influence ischemic shifts of K+i and Na+i content.

Animals↗
PubMed1986

[Sclerodermiform porphyria].

We give a retrospective survey on the clinical, histological, biochemical, and pathogenetical aspects of sclerodermiform changes rarely accompanying porphyria cutanea tarda (PCT). Sclerodermiform changes were seen in 12 patients (2% of all our PCT cases). In these patients, no correlation was found between the severity of the dermatological signs and symptoms and the degree of disturbance in the porphyrin metabolism. Biochemical remission was not accompanied by improvement of the sclerodermiform changes. The proportion of porphyrins with 4 or 5 COOH-groups was higher than that of PCT patients without sclerosis. The findings are consistent with the view that the development of sclerodermiform changes cannot be merely explained by phototoxic reactions, but the "dark-effect" of the porphyrins may also play an important role in the pathogenesis.

Actin Cytoskeleton↗
PubMed1986

Effect of BN 52021, a specific PAF-acether antagonist, on cardiac anaphylaxis in Langendorff hearts isolated from passively sensitized guinea-pigs.

Hartley guinea-pigs were sensitized passively with antiovalbumin rabbit serum. Their isolated perfused hearts responded to the specific antigen with a marked decrease in contractile force, increase in perfusion pressure, and rhythm disturbances. All these impairments except tachycardia were decreased by BN 52021, a specific PAF-acether receptor antagonist, applied in a constant infusion before ovalbumin challenge. These findings suggest that PAF-acether plays a major role as mediator in cardiac anaphylaxis, and BN 52021 may be a valuable therapeutic agent in allergic conditions.

Anaphylaxis↗
PubMed1986

Interaction of calcium antagonists with beta-adrenoceptor blocking agents.

Responsiveness to verapamil, the best studied calcium antagonist, was examined in cardiac preparations of rabbits pretreated with beta-adrenoceptor blockers (propranolol 2 mg/kg or oxprenolol 4 mg/kg s.c.) twice daily for either one or six weeks. Using this dose-regimen, the degree of cardiac beta-adrenoceptor blockade in conscious rabbits was substantial and similar for propranolol and oxprenolol. When administered for one week, neither propranolol nor oxprenolol affected to any marked extent the electrical and mechanical response to verapamil, diltiazem or fendiline in tissues isolated from various parts of the heart. In contrast, pretreatment with propranolol for six weeks resulted in a significant aggravation of the negative inotropic effect of verapamil in both atrial and ventricular muscle, and the verapamil-induced delay in atrio-ventricular and intra-ventricular conduction also became more pronounced. The same long-term administration of oxprenolol, one of the beta-blockers with "intrinsic" sympathomimetic activity, did not alter the atrial or ventricular contractile response to verapamil and did not significantly increase the lengthening of atrio-ventricular conduction time occurring in the presence of verapamil. It is concluded that from the point of view of adverse direct cardiac interactions with verapamil prolonged administration of oxprenolol appears to be less dangerous than chronic treatment with propranolol. It is also assumed that in those cases in which acute administration of verapamil may be necessary, concomitant chronic blockade of cardiac beta-adrenoceptors is less dangerous if drugs known to possess not only beta-adrenoceptor blocking properties, but also some "intrinsic" sympathomimetic activity are applied.

Adrenergic beta-Antagonists↗
PubMed1986

Disturbance of motoric function as behavioral measure of impaired cerebral circulation in mice.

Aim of the present experiments was to elaborate an experimental model exhibiting the functional consequences of a moderate impairment of cerebral circulation sensitive enough for testing the long-term cerebroprotective effect of different drugs. In preliminary experiments mice survived unilateral occlusion of the carotid artery. This intervention, however, severely impaired the motor skill of the animals as measured by their activity on the rotating treadmill. Motimeter activity was also diminished following unilateral carotid occlusion. Somewhat unexpectedly, a more complex pattern of learned behavior in a one-trial learning passive avoidance paradigm was only modestly affected by unilateral carotid occlusion. Papaverine (2.0 mg/kg) normalized the motor incoordination measured on the rotating treadmill. The data suggest that impaired motoric function, as a result of unilateral carotid occlusion, might be a useful experimental tool to analyse functional consequences of impaired cerebral circulation and a sensitive test for screening of drugs with presumed cerebroprotective action.

Animals↗
PubMed1986

Sympathetic neural mechanisms in cardiac arrhythmias.

In the present experiments the dominant role in the genesis of arrhythmias of stimulation of beta adrenoceptors over that of alpha adrenoceptors has been demonstrated by: (i) infusion of catecholamines in the isolated right ventricular Purkinje fiber preparation of rabbits; and (ii) by subepicardial microinfusion of these substances to anesthetized thoracotomized dogs. Activation of the latent pacemaker areas by local myocardial ischemia was shown. Catecholamine-induced arrhythmias also resulted from premature excitation of the working myocardium as a consequence of an interaction of Purkinje firing and excitation originating from higher pacemaker areas.

Animals↗
PubMed1986

Membrane phospholipid and fatty acid changes in the mitochondrial and sarcolemmal fractions of the heart in adjuvant arthritic rats.

Adjuvant arthritis was found to induce changes in phospholipid and fatty acid composition as well as in membrane fluidity of mitochondrial and sarcolemmal fractions in the rat heart. In the sarcolemmal fraction, phosphatidylcholine content was decreased, while phosphatidylserine, phosphatidylinositol and the lysocompounds of phospholipids were increased. Mitochondria isolated from the heart of rats with adjuvant disease contained less linoleic acid than control samples. Docosatetraenoic acid and docosahexaenoic acid levels were shown to be increased in both mitochondrial and sarcolemmal fractions of the heart in treated animals. Electron spin resonance studies indicated that the break points of the curves obtained by plotting the order parameters against temperature changes were slightly shifted to lower temperature region in both subcellular fractions of arthritic rat hearts. As compared to the control values, membrane fluidity was increased both in mitochondrial and sarcolemmal fractions. The relationship of these alterations to our previous findings that adjuvant arthritis protected the rats against fatal post-infarctions arrhythmias needs further elucidation.

Animals↗
PubMed1986

Pharmacotherapy of sudden cardiac death due to acute myocardial ischaemia. Experimental and clinical experience.

A critical review of experimental studies aiming to determine the effect of drugs in the prevention of sudden cardiac death. They include antiischaemic drugs, the drugs influencing transmembrane ion transport, those altering the phospholipid structure of the myocardial membrane as well as the medicaments improving blood rheology, preventing thrombosis, cytoprotective drugs and thrombolytic therapy.

Animals↗