Biomedical subjects

András Farkas

Publications and source records attributed to András Farkas.

12 recordsLinked to original sources

PubMed2006

Importance of extracardiac alpha1-adrenoceptor stimulation in assisting dofetilide to induce torsade de pointes in rabbit hearts.

In anaesthetized rabbits, alpha(1)-adrenoceptor stimulation increases the propensity of repolarization-prolonging drugs to induce torsade de pointes ventricular tachycardia. However, it is not known whether the stimulation of intracardiac alpha(1)-adrenoceptors, or the increased ventricular stretch caused by extracardiac alpha(1)-adrenoceptor-mediated peripheral vasoconstriction and increased resistance, are the sensitizing factors. Accordingly, this study investigated whether a sustained load-induced left ventricular stretch or stimulation of the intracardiac alpha(1)-adrenoceptors with 100 nM methoxamine, or the co-application of these two, can assist dofetilide (100 nM) to elicit torsade de pointes in isolated Langendorff-perfused, rabbit hearts. In the stretched hearts, a constant high level of stretch was produced by a water-filled left ventricular balloon inflated to a volume of 1.4 ml, whereby the systolic and end-diastolic pressures virtually did not exceed the physiological range (<or=157+/-11 mm Hg and <or=9+/-2 mm Hg, respectively; mean+/-S.E.M.). Perfusion with dofetilide prolonged the QT interval significantly and indifferently in all hearts. Neither this stretch nor methoxamine nor the in combination affected the QT interval, the heart rate or the coronary flow. Interestingly, neither the stretch ('dofetilide+stretch' group, n=8 hearts), nor methoxamine ('dofetilide+methoxamine' group, n=8 hearts), nor the in combination ('dofetilide+stretch+methoxamine' group, n=8 hearts) elevated the incidence of torsade de pointes as compared with the 'dofetilide alone' group (n=9 hearts) (0%, 25%, 0%, versus 44%, respectively). In conclusion, neither a sustained load-induced stretch nor alpha(1)-adrenoceptor stimulation nor the in combination assisted dofetilide to induce torsade de pointes in isolated rabbit hearts, suggesting the importance of extracardiac alpha(1)-adrenoceptor stimulation in this phenomenon.

Adrenergic alpha-1 Receptor Agonists↗

PubMed2005

[A case of absent right and persistent left superior vena cava: echocardiographic diagnosis].

A 49-year-old man underwent transthoracic echocardiography for atypical chest pain. A dilated coronary sinus was found and venous contrast echocardiography raised the suspicion of absent right and persistent left superior vena cava. Transesophageal echocardiography showed no presence of right superior vena cava. The echocardiographic findings were confirmed by upper venous digital subtraction cavography.

Angiography, Digital Subtraction↗

PubMed2004

Effects of octreotide on acute necrotizing pancreatitis in rabbits.

AIM: To assess the role of oxygen-derived free radicals and cytokines in the pathogenesis of taurocholic acid-induced acute pancreatitis, and to evaluate the preventive effects of octreotide towards the development of acute pancreatitis. METHODS: Acute pancreatitis was induced in male New Zealand white rabbits by retrograde injection of 0.8 mL/kg.b.m. of 50 g/L sodium taurocholate (NaTC) in the pancreatic duct. Sham-operated animals served as control. Octreotide 1 mg/kg.b.m. was administered subcutaneously before the induction of pancreatitis. Blood was taken from the jugular vein before and at 1, 3, 6, 12 and 24 h after pancreatitis induction. Serum activities of amylase, IL-6 and TNF-alpha and levels of malonyl dialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (Mn-, Cu-, and Zn-SOD) in pancreatic tissue were measured. RESULTS: Serum TNF-alpha and IL-6 levels increased significantly 3 h after the onset of pancreatitis, and then returned to control level. The tissue concentration of MDA was significantly elevated at 24 h, while the GSH level and GP-x, catalase, Mn-SOD, Cu-, Zn-SOD activities were all significantly decreased in animals with pancreatitis as compared to the control. Octreotide pretreatment significantly reversed the changes in cytokines and reactive oxygen metabolites. Octreotide treatment did not alter the serum amylase activity and did not have any beneficial effects on the development of histopathological changes. CONCLUSION: Oxygen-derived free radicals and proinflammatory cytokines are generated at an early stage of NaTc-induced acute pancreatitis in rabbits. Prophylactic octreotide treatment can prevent release of cytokines and generation of reactive oxygen metabolites, but does not have any beneficial effects on the development of necrotizing pancreatitis.

Animals↗

PubMed2003

Prevention of clofilium-induced torsade de pointes by prostaglandin E2 does not involve ATP-dependent K+ channels.

Drugs that prolong the QT interval can trigger the life-threatening arrhythmia, torsade de pointes, but there is a poor correlation between the extent of QT prolongation and the occurrence of torsade de pointes. The clinical status of a patient may modify the arrhythmogenicity of drugs; thus, we have investigated whether a mediator of fever and inflammation, prostaglandin E(2), alters the proarrhythmic effects of clofilium. In pentobarbitone-anaesthetized, open-chest, alpha-adrenoceptor-stimulated rabbits, prostaglandin E(2) 0.28, 0.84 and 2.80 nmol kg(-1) min(-1), infused into the left ventricle, reduced the incidence of torsade de pointes from 50% in controls to 20%, 20% and 0%, respectively (n=10 per group). Pretreatment with glibenclamide (10 micromol kg(-1)) did not alter the antiarrhythmic effect of prostaglandin E(2) (2.80 nmol kg(-1) min(-1)). These results indicate that prostaglandin E(2) prevents drug-induced torsade de pointes and that this action of prostaglandin E(2) is not mediated via opening of ATP-dependent K(+) channels (K(ATP)).

Adenosine Triphosphate↗

PubMed2003

Does QT widening in the Langendorff-perfused rat heart represent the effect of repolarization delay or conduction slowing?

It has been suggested that class I antiarrhythmic drugs and ischemia can widen the QT interval in the Langendorff-perfused rat heart preparation as a consequence of slowed ventricular conduction. If this were so, it would undermine the clinical relevance of the preparation and its effectiveness as an antiarrhythmic bioassay. To test this, the authors determined whether three different class I drugs could prolong QT in the preparation and whether this effect was augmented by ischemia and elevation of the potassium (K+) content of the perfusion solution. Baseline drug-free QT intervals correlated inversely with the K+ content (3 microM vs. 5 mM). QT intervals widened during the first 3-5 minutes of ischemia (P < 0.05), then returned gradually to baseline. Lidocaine (3.88 microM and 12.93 microM) had no effect on the QT interval before or during ischemia, whereas quinidine (7.90 microM but not 0.79 microM) and flecainide (1.48 microM but not 0.74 microM) caused QT widening before and during ischemia (P < 0.05). Elevating perfusion solution K+ content from 3 microM to 5 mM reduced the QT-widening effects of quinidine and flecainide (P < 0.05). Because lidocaine, a relatively selective sodium (Na+) channel blocker, failed to widen QT interval whereas quinidine and flecainide (combined Na+ and K+ channel blockers) did so, and because K+ elevation reduced rather than potentiated the drug-induced QT widening, it is unlikely that Na+ channel blockade and conduction slowing play any role in ischemia- or class I drug-induced QT widening in this model.

Animals↗

PubMed2002

Plasma levels of IL-6 correlate with hemodynamic abnormalities in acute pancreatitis in rabbits.

OBJECTIVE: To examine the relationship between plasma cytokine levels and cardiac and hemodynamic function. DESIGN: Measurement of cytokines and the systolic (left ventricular dimensions, heart rate, and cardiac output) and diastolic (early and late transmitral peak flow velocity: E and A-waves and their ratio) functions of the left ventricle (assessed by echocardiography) in rabbits. SETTING AND INTERVENTIONS: Laboratory and echocardiographic analyses were performed at baseline and at 1, 3, 6, 12, and 24 h after acute necrotizing pancreatitis induction (Group ANP), in rabbits after somatostatin pretreatment (Group S-ANP) and in sham-operated controls (Group C). MEASUREMENTS AND RESULTS: Left ventricular dilatation occurred at 6 h and cardiac output was increased 3 h after induction of acute necrotizing pancreatitis. Somatostatin pretreatment mitigated the left ventricular enlargement and filling abnormalities. Plasma level of IL-6 was increased significantly 3 h after pancreatitis induction, but to a lesser extent in Group S-ANP, while somatostatin prevented TNFalpha release (IL-6: Group ANP: 0, 0, 518+/-139, 956+/-125, 373+/-48, and 122+/-37 pg/ml; Group S-ANP: 0, 0, 191+/-68, 261+/-49, 23+/-13, and 0 pg/ml; TNFalpha: Group ANP: 88+/-42, 371+/-40, 2963+/-291, 276+/-30, 197+/-106, and 23+/-14 U/l; Group S-ANP: 91+/-34, 41+/-25, 68+/-42, 25+/-9, 0, and 0 U/ml). The increase in plasma level of IL-6 correlated significantly with left ventricular end-diastolic diameter and volume, cardiac output, and diastolic dysfunction. CONCLUSIONS: Plasma levels of IL-6, but not TNFalpha correlate with cardiac output and left ventricular filling characteristics in acute pancreatitis. Somatostatin pretreatment improves the cardiac and hemodynamic changes, probably through the decrease in cytokine release.

Animals↗

PubMed2002

TiO2-based photocatalytic degradation of 2-chlorophenol adsorbed on hydrophobic clay.

The combination of adsorption and heterogeneous photocatalysis has been investigated as a promising technology for the removal of organic water pollutants. A laboratory study of the removal and decomposition of 2-chlorophenol (2-CP) as a toxic organic pollutant was carried out under various conditions with an organophilized clay mineral (hexadecylpyridinium chloride-modified montmorillonite; HDPM) as adsorbent and Degussa P25 TiO2 as photocatalyst. Three different oxidation processes leading to the degradation of 2-CP were compared: direct photolysis, heterogeneous photocatalysis in a TiO2 suspension, and the decomposition of substrate adsorbed on HDPM in the presence of TiO2. Both the degradation of 2-CP and the formation of intermediates were analyzed by HPLC, the total organic carbon content and the total organic and inorganic chloride contents were measured to monitor the mineralization process, and X-ray diffraction and thermoanalytical measurements were made to characterize the hydrophobic clay adsorbent. The heterogeneous photocatalytic degradation of dissolved (2-CP/UV/TiO2) and desorbed 2-CP (2-CP/HDPM/UV/TiO2) appeared to be equally efficient, whereas direct photolysis of 2-CP was far less efficient in the oxidative destruction. HDPM proved to be a suitable adsorbent, capable of adsorbing toxic organics from water. It was demonstrated that the adsorbent (at relatively high concentration) did not decrease the rate of mineralization of 2-CP. The results confirmed that the adsorbent retains its structure and composition during the mineralization process, and thus it can be reused without regeneration. The combination of adsorption and heterogeneous photocatalysis studied may be an efficient and economical means of accumulating, removing, and oxidizing organic water contaminants, and its application is in accordance with the growing environmental demands.

Adsorption↗

PubMed2002

Limited induction of torsade de pointes by terikalant and erythromycin in an in vivo model.

The proarrhythmic activities of the selective I(Kr) blocker erythromycin and the less selective K(+) channel blockers, terikalant and clofilium, have been compared in an alpha(1)-adrenoceptor-stimulated, anaesthetized rabbit model. Terikalant (2.5, 7.5 and 25 nmol kg(-1) min(-1); n = 10), erythromycin (133, 400 and 1330 nmol kg(-1) min(-1); n = 8), clofilium (20, 60 and 200 nmol kg(-1) min(-1); n=10) or vehicle (n = 8) was infused intravenously over 19 min and there was a 15-min interval between each infusion [corrected]. QT and QTc intervals, and epicardial monophasic action potential duration were prolonged significantly (and to a similar extent) only by clofilium and terikalant. The total incidences of torsade de pointes were 60%*, 20%, 0% and 0% in clofilium-, terikalant-, erythromycin- and vehicle-treated animals, respectively (*P < 0.05 compared to vehicle control). In conclusion, terikalant exerted mild proarrhythmic activity though it prolonged repolarisation markedly. Despite being given in high doses, erythromycin neither prolonged repolarisation nor induced proarrhythmia.

Action Potentials↗

PubMed2002

Proarrhythmic effects of intravenous quinidine, amiodarone, D-sotalol, and almokalant in the anesthetized rabbit model of torsade de pointes.

The proarrhythmic effects of four antiarrhythmic agents were examined during alpha1-adrenoceptor stimulation in chloralose-anesthetized rabbits. Each dose of almokalant (26, 88, and 260 microg/kg), D-sotalol, quinidine, or amiodarone (each 3, 10, and 30 mg/kg) was infused i.v. over 5 min and there was a 20-min interval between each infusion. D-sotalol and almokalant evoked torsade de pointes (TdP) and other arrhythmics, frequently. The incidences of TdP were 0, 50, and 40% after administering the first, second, and third doses of the nonselective I(Kr) inhibitor D-sotalol, respectively. Similarly, these values were 20, 40, and 33% after administering the first, second, and third doses, respectively, of the selective I(Kr) inhibitor almokalant. Quinidine elicited only a few arrhythmics, but not TdP. Quinidine, D-sotalol, and almokalant evoked conduction blocks in a dose-related manner (p < 0.05) and prolonged QT and QT(c) intervals (p < 0.05). Amiodarone neither prolonged QT and QT(c) nor evoked ventricular tachyarrhythmias, blocks, or other proarrhythmias. In conclusion, these results show no direct correlation between the occurrence of TdP and the infusion rate or dose of anti-arrhythmics. Furthermore, the lack of TdP with quinidine warns of false-negative results in the applied model.

Adrenergic alpha-1 Receptor Agonists↗

PubMed2002

Limited antifibrillatory effectiveness of clinically relevant concentrations of class I antiarrhythmics in isolated perfused rat hearts.

The Langendorff-perfused rat heart with regional ischemia is increasingly used for evaluating drugs for prevention of phase-1, ischemia-induced ventricular fibrillation (VF). Surprisingly, the effectiveness of Class I antiarrhythmics has not been characterized in this model. One lower and one higher concentration of quinidine (0.79 and 7.90 microM), lidocaine (3.88 and 12.93 microM), and flecainide (0.74 and 1.48 microM), representing the peak unbound plasma and total blood concentrations, respectively, at "therapeutic" dosage, were evaluated. The left main coronary artery was occluded for 30 min to elicit phase-1 VF, after which reperfusion-induced VF was examined. In hearts perfused with Krebs' solution containing 3 mM K(+), the higher concentrations of quinidine and lidocaine reduced the incidence of phase-1 VF from 92% to 0% and 17% respectively, (each p < 0.05). The lower drug concentrations were ineffective. Flecainide was equi-effective at low and high concentrations, with VF incidence reduced from 92% to 17% (p < 0.05). Neither low nor high concentrations of any of the drugs affected the incidence of reperfusion-induced VF. Using hearts perfused with Krebs' containing 5 mM K(+), sufficient to substantially reduce control phase-1 VF incidence, the experiment was repeated to test for possible proarrhythmic activity. None of the three drugs increased arrhythmia incidence. In this model, it was not possible to suppress ischemia-induced and reperfusion-induced VF with flecainide, lidocaine, or quinidine at concentrations equivalent to peak unbound plasma levels after clinical administration. This may explain the lack of clinical benefit with these drugs against sudden cardiac death. Because none of the drugs were proarrhythmic in ischemic hearts in which arrhythmia susceptibility had been lowered by high K(+), it would seem that clinical proarrhythmia seen with these drugs may not be related to exacerbation of phase-1, ischemia-induced VF.

Animals↗

PubMed2002

[Late reconstructive surgery for cloaca malformations].

The rarity of cloacal anomalies, the wide range of anatomical variants, and the number of different operations mean that successful management of a patient (neonate or child) with this condition is one of the greatest challenges for paediatric surgeons. The authors describe the complex corrections of 3 patients with cloacal malformation (age 10-13 years). The cloacal malformations were not diagnosed at neonatal age and therefore only the anorectal agenesis was corrected at the first stage. The authors strongly recommend that all components of this anomaly (urethra, vagina and anorectum) should be managed in one step. Because of the rarity and complexity of cloacal malformations, the anomaly should be operated on only in specialised centres.

Adolescent↗

PubMedDate not supplied

How to measure electrocardiographic QT interval in the anaesthetized rabbit.

Many drugs prolong QT or QU intervals [QT(U)] in the electrocardiogram (ECG), and this may be associated with the generation of drug-induced torsades de pointes. Therefore, it is essential to assess the ability of the newly developed drugs to prolong QT(U) interval. For this purpose, both in vivo and in vitro rabbit models are frequently used. However, it is very difficult to locate the end of the QT(U) interval in most rabbit ECGs when repolarisation is delayed, as the shape of the T and U waves may be deformed. In addition, as the heart rate of the rabbit is very high, the T (or U) wave may overlap the P wave or even the QRS complex of the following sinoatrial beat. In these circumstances, application of the "extrapolation method" makes it possible to determine the length of the QT(U) interval. This article describes the extrapolation method, shows ECG examples of typical T and U waves in the anaesthetized rabbit, and makes an attempt to provide a useful guide for researchers to measure reliably and reproducibly the duration of the QT(U) interval in rabbit studies.

Anesthesia↗