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1.

001-es BibID:BIBFORM032954
Első szerző:Bányász Tamás (élettanász)
Cím:Frequency-dependent characteristics of human cardiac muscle / Tamás Bányász, János Magyar, Péter Szigligeti, Csaba Pankucsi, András Varró, Péter P. Nánási
Dátum:1997
Megjegyzések:OBJECTIVES: To characterize the steady state frequency-dependent properties and restitution kinetics of action potential duration (APD) in isolated human atrial and ventricular cardiac muscle preparations. MATERIALS AND METHODS: Conventional microelectrode techniques were used to record action potentials in preparations of human left ventricular muscle and right atrial appendages under steady state conditions or after abrupt changes in cycle length, ie, following increasingly longer diastolic intervals (DI). Restitution relations were generated by plotting APD against the respective DI. Restitution relations were fitted to multiexponential functions. RESULTS: Restitution of APD at 90% repolarization in ventricular preparations, paced at a basic cycle length (BCL) of 750 ms, were fitted as the sum of four exponentials, having time constants of 42.8 ms, 139 ms, 1.34 s and 16 s. Similar results were obtained for restitution of values of APD at 50% repolarization. In atrial preparations, restitution kinetics were characterized by three exponentials with time constants of 154 ms, 1.52 s and 25.5 s (BCL of 750 ms). The very fast component of restitution, observed in ventricular muscle, was apparently missing in atrial fibres. When atrial preparations were paced at a longer BCL of 5000 ms, no change in time constants of restitution was observed; however, the amplitudes of the second and third atrial components decreased significantly compared with preparations paced at a BCL of 750 ms. CONCLUSIONS: Comparing the time constant values estimated for restitution with the reported kinetic parameters of cardiac ion channels, it may be speculated that the first component of restitution in ventricular muscle is attributed to the recovery of L-type calcium current from inactivation. The lack of this very rapid component in atrial muscle can be explained by the parallel recovery of the calcium current and the transient outward potassium current, prominent in atrial myocardium. The second ventricular component (first in atrium) may be due to the time-dependent deactivation of the delayed rectifier potassium current. The third and fourth ventricular components (second and third components, respectively, in the atrium) are probably related to transient changes in intracellular ionic composition.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Experimental And Clinical Cardiology 2 : 3 (1997), p. 205-209. -
További szerzők:Magyar János (1961-) (élettanász) Szigligeti Péter Pankucsi Csaba (farmakológus) Varró András (1954-) (farmakológus, klinikai farmakológus) Nánási Péter Pál (1956-) (élettanász)
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2.

001-es BibID:BIBFORM030340
035-os BibID:WOS:A1996VM24200008 PMID:8901455
Első szerző:Kecskeméti Valéria
Cím:Comparative study of cardiac electrophysiological effects of atrial natriuretic peptide / Valéria Kecskemeti, Pál Pacher, Csaba Pankucsi, Péter P. Nanasi
Dátum:1996
ISSN:0300-8177
Megjegyzések:The effects of atrial natriuretic peptide (ANP) on action potential characteristics were studied in various (human, rabbit, guineapig) atrial and guinea-pig right ventricular papillary muscles. ANP (1-100 nM) did not modify the resting membrane potential nor the maximum rate of depolarization phase (V-max). Up to 10 nM, ANP dose-dependently decreased the action potential amplitude both in guinea-pig atrial and ventricular muscles, but it did not affect this parameter in the other atrial preparations. ANP caused a dose-dependent, marked decrease of action potential duration (APD) in practically every cardiac preparation studied (exception of guinea-pig left atrium). The strongest effect on APD can be observed in human atrial and guinea-pig ventricular fibers. The K+ channel blocker 4-aminopyridine (1 mM) and the ATP-dependent K+ channel inhibitor glibenclamide (10 mu M) prevented the effect of ANP on APD in both ventricular atrial preparations. ANP prevented the appearance of isoprenaline (0.5 mu M) induced slow AP in K+ depolarized myocardium. The present data suggest that ANP may inhibit the slow inward Ca2+ channel activity and facilitate the K+ channel activity.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Molecular and Cellular Biochemistry. - 160-161 (1996), p. 53-59. -
További szerzők:Pacher Pál Pankucsi Csaba (farmakológus) Nánási Péter Pál (1956-) (élettanász)
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3.

001-es BibID:BIBFORM030341
035-os BibID:10684401
Első szerző:Lathrop, David A.
Cím:Differences in the effects of d- and dl-sotalol on isolated human ventricular muscle : electromechanical activity after beta-adrenoceptor stimulation / David A. Lathrop, András Varró, Péter P. Nánási, Ilona Bodi, Eric Takyi, Csaba Pankucsi
Dátum:1996
ISSN:1074-2484 (Linking)
Megjegyzések:BACKGROUND: The racemate of sotalol (dl-sotalol) and its dextrorotatory isomer(d-sotalol) are equally effective in increasing isolated cardiac action potentialdurations. dl-Sotalol, however, is reported to be more effective than d-sotalolin increasing ventricular effective refractoriness following coronary arteryocclusion. These differences are attributed to the beta-adrenergic blockingproperties of dl-sotalol. We wished to determine if in isolated human ventricularmuscle preparations the effects of 30 microM d0 and dl-sotalol could be modifiedby preexposure to 1 microM isoproterenol. METHODS AND RESULTS: Microelectrodeswere used to record action potential duration (APD) in the presence and absenceof isoproterenol during continuous pacing. Preparations were obtained fromexplanted hears of transplant recipients suffering idiopathic cardiomyopathies.Without isoproterenol, APD measured at 90% of repolarization (APD(90)) wasIsoproterenol alone, prior to sotalol exposure, tended to shorten APD(90) in thetwo groups first exposed to this beta-adenoceptor agonist and subsequently28.5 ms, NS). CONCLUSIONS: The beta-adrenergic blocking properties of dl-sotalolmay be important in determining antiarrhythmic efficacy when tonic sympatheticnervous activity is high.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Journal of cardiovascular pharmacology and therapeutics. - 1 : 1 (1996), p. 65-74. -
További szerzők:Varró András (1954-) (farmakológus, klinikai farmakológus) Nánási Péter Pál (1956-) (élettanász) Bódi Ilona Takyi, Eric Pankucsi Csaba (farmakológus)
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4.

001-es BibID:BIBFORM030258
035-os BibID:WOS:000181565400020
Első szerző:Magyar János (élettanász)
Cím:Differential effects of fluoxetine enantiomers in mammalian neural and cardiac tissues / János Magyar, Zoltán Rusznák, Csaba Harasztosi, Ágnes Körtvély, Pál Pacher, Tamás Bányász, Csaba Pankucsi, László Kovács, Géza Szűcs, Péter P. Nánási, Valéria Kecskeméti
Dátum:2003
ISSN:1107-3756
Megjegyzések:Racemic fluoxetine is a widely used SSRI antidepressant compound having also anticonvulsant effect. In addition, it was shown that it blocked several types of voltage gated ion channels including neural and cardiac calcium channels. In the present study the effects of enantiomers of fluoxetine (R(-)-fluoxetine and S(+)-fluoxetine) were compared on neuronal and cardiac voltage-gated Ca2+ channels using the whole cell configuration of patch clamp techniques, and the anticonvulsant action of these enantiomers was also evaluated in a mouse epilepsy model. In isolated pyramidal neurons of the dorsal cochlear nucleus of the rat the effect of fluoxetine (S(+), R(-) and racemic) was studied on the Ca2+ channels by measuring peak Ba2+ current during ramp depolarizations. All forms of fluoxetine reduced the Ba2+ current of the pyramidal cells in a concentration-dependent manner, with a K, value of 22.3 +/- 3.6 muM for racemic fluoxetine. This value of K, was higher by one order of magnitude than found in cardiac myocytes with fluoxetine enantiomers (2.4 +/- 0.1 and 2.8 +/- 0.2 muM). Difference between the effects of the two enantiomers on neuronal Ba2+, current was observed only at 5 muM concentration: R(-)-fluoxetine inhibited 28 +/- 3% of the peak current, while S(+)-fluoxetine reduced the current by 18 +/- 2% (n=13, P<0.05). In voltage clamped canine ventricular cardiomyocytes both enantiomers of fluoxetine caused a reversible concentration-dependent block of the peak Ca2+ current measured at 0 mV. Significant differences between the two enantiomers in this blocking effect was observed at low concentrations only: S(+)-fluoxetine caused a higher degree of block than R(-)-fluoxetine (56.3 +/- 2.2% versus 49.1 +/- 2.2% and 95.5 +/- 0.9% versus 84.5 +/- 3.1% block with 3 and 10 &mu;M S(+) and R(-)-fluoxetine, respectively, P<0.05, n=5). Studied in current clamp mode, micromolar concentrations of fluoxetine shortened action potential duration of isolated ventricular cells, while higher concentrations also suppressed maximum velocity of depolarization and action potential amplitude. This shortening effect was significantly greater in the case of S(+) than R(-)-fluoxetine at 1 and 3 muM concentrations, whereas no differences in their effects on depolarization were observed. In pentylenetetrazole-induced mouse epilepsy model fluoxetine pretreatment significantly increased the 60 min survival rate, survival duration and seizure latency. These effects were more pronounced with the R(-) than the S(+) enantiomer. The results indicate that fluoxetine exerts much stronger suppressive effect on cardiac than neuronal calcium channels. At micromolar concentrations (between 1 and 10 muM) R(-)-fluoxetine is more effective than the S(+) enantiomer on neuronal, while less effective on cardiac calcium channels. The stronger anticonvulsant effect of the R(-) enantiomer may, at least partially, be explained by these differences. Used as an antidepressant or anticonvulsant drug, less severe cardiac side-effects are anticipated with the R(-) enantiomer.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:International Journal of Molecular Medicine. - 11 : 4 (2003), p. 535-542. -
További szerzők:Rusznák Zoltán (1965-) (élettanász) Harasztosi Csaba Körtvély Ágnes Pacher Pál Bányász Tamás (1960-) (élettanász) Pankucsi Csaba (farmakológus) Kovács László (1939-) (élettanász) Szűcs Géza (1948-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Kecskeméti Valéria
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5.

001-es BibID:BIBFORM030339
035-os BibID:PMID: 8899061 WOS:A1996VL12100005
Első szerző:Nánási Péter Pál (élettanász)
Cím:Electrical restitution in rat ventricular muscle / P. P. Nanasi, Cs. Pankucsi, T. Banyasz, P. Szigligeti, J. Gy. Papp, A. Varro
Dátum:1996
ISSN:0001-6772
Megjegyzések:The mechanism of electrical restitution was studied in isolated rat ventricular muscle using drugs that inhibit specific ion currents. The effect of transient changes in cytosolic Ca concentration and Na/Ca exchange in relation to the restitution process was also studied in single ventricular cardiomyocytes. Conventional microelectrode techniques were applied to record action potentials having gradually increasing coupling intervals. each evoked following a train of stimuli with a frequency of 1 Hz. ion currents were recorded from enzymatically isolated cells using the whole cell parch clamp technique. Ca transients were monitored in myocytes loaded with the fluorescent dye, indo-1. The electrical restitution process in multicellular rat ventricular preparations at 37 degrees C was described as a sum oi three exponential components: an early positive component. a subsequent fast negative component and a late negative component. having time constants of 21.9 +/- 1.9, 73.1 +/- 6.0 and 1053 +/- 61 ms, respectively (n = 9). Inhibition of the transient outward K current the delayed rectifier K current. or the chloride current did not substantially alter these time constants, The early positive and fast negative components were fully abolished by nifedipine or MnCl2. In the presence of caffeine. the fast negative component was absent. while the time constant of the early positive component increased to 39.5 +/- 5.8 ms (n = 5). In single myocytes loaded with indo-1, the Ca transients decayed with a time constant of 151 +/- 12 ms at room temperature (n = 5). These Ca transients were accompanied by inward current tails. identified as a Na/Ca exchange current. having a decay time constant of 140 +/- 4.5 ms. It is concluded that electrical restitution in rat ventricular muscle is relatively little affected by recovery from voltage-dependent inactivation of ion channels. it is rather governed by transient changes in cytosolic Ca concentration possible via Ca-dependent inactivation of the L-type Ca current and activation of the Na/Ca exchange current.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Acta Physiologica Scandinavica. - 158 : 2 (1996), p. 143-153. -
További szerzők:Pankucsi Csaba (farmakológus) Bányász Tamás (1960-) (élettanász) Szigligeti Péter Papp Gy. Julius (Szeged) Varró András (1954-) (farmakológus, klinikai farmakológus)
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6.

001-es BibID:BIBFORM030338
035-os BibID:(WoS)A1996UY14300002 (Scopus)0029798762 (PMID)8842570
Első szerző:Nánási Péter Pál (élettanász)
Cím:Electrical restitution in diseased human ventricular myocardium / Péter P. Nanasi, Andras Varro, Csaba Pankucsi, Péter Homolay, Timothy K. Knilans, László Kovacs, Gyula J. Papp, David A. Lathrop
Dátum:1996
ISSN:0144-5979
Megjegyzések:Action potential configuration and electrical restitution were studied in diseased human ventricular muscle by comparing the characteristics of hypertrophic (HYP) and dilated (DIL) human ventricular preparations. Conventional microelectrode techniques were used to evaluate action potentials evoked at increasingly longer diastolic intervals, The steady-state action potential duration (APD(90)) was significantly longer in DIL than in HYP preparations (393+/-5 ms, n=4 and 296+/-11 ms, n=4, respectively; P<0.001, mean+/-SEM). In the dilated preparations studied at long diastolic intervals, the initial period of rapid repolarization (phase 1) was absent, and the rate of final repolarization (phase 3) was reduced. Electrical restitution relations in these preparations were fitted as the sum of two exponentials, The time constant of the fast component was significantly longer in DIL than in HYP preparations (242+/-9 ms and 121+/-4 ms, respectively; P<0.001). No difference was observed in the time constants for the slow component of restitution in the two groups. Electrical restitution was also studied in single human ventricular myocytes by using patch clamp techniques. The initial 600 ms period of restitution was fitted in these cells to a monoexponential function. The time constant for this period of the restitution relation was significantly longer, while the estimated amplitude of this early rising phase was significantly lower in human cells obtained from DIL hearts than the respective parameters obtained in the healthy canine and guinea pig cells also examined, The observed changes in the restitution kinetics of the dilated human heart are, likely, the consequence of alterations in the ionic currents that underlie the cardiac action potential.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
egyetemen (Magyarországon) készült közlemény
Megjelenés:Clinical Physiology. - 16 : 4 (1996), p. 339-351. -
További szerzők:Varró András (1954-) (farmakológus, klinikai farmakológus) Pankucsi Csaba (farmakológus) Homolay Péter (1947-1999) (mellkassebész, szívsebész) Knilans, Timothy K. Kovács László (1939-) (élettanász) Papp Gy. Julius (Szeged) Lathrop, David A.
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7.

001-es BibID:BIBFORM030266
035-os BibID:WOS:000084701100010
Első szerző:Pacher Pál
Cím:Electrophysiological effects of fluoxetine in mammalian cardiac tissues / Pál Pacher, János Magyar, Péter Szigligeti, Tamás Bányász, Csaba Pankucsi, Zsuzsanna Korom, Zoltán Ungvári, Valéria Kecskeméti, Péter P. Nánási
Dátum:2000
ISSN:0028-1298
Megjegyzések:Fluoxetine is a widely used antidepressant compound having selective serotonin reuptake inhibitor properties. In this study, the actions of fluoxetine were analyzed in guinea pig, rat, rabbit and canine ventricular myocardiac preparations using conventional microelectrode and whole cell voltage clamp techniques. Low concentrations of fluoxetine (1-10 mu mol/l) caused significant shortening of action potential duration (APD) and depression of the plateau potential in guinea pig and rabbit papillary muscles and single canine ventricular myocytes. In rat papillary muscle, APD was not affected by fluoxetine (up to 100 mu mol/l), however, the drug decreased the force of contraction with EC50 of 10 mu mol/l. Fluoxetine (10 mu mol/l) also decreased the maximum velocity of depolarization and action potential overshoot in each species studied. At this concentration no effect was observed on the resting membrane potential; high concentration (100 mu mol/l), however, caused depolarization. In voltage clamped canine ventricular myocytes, fluoxetine caused concentration-dependent block of the peak Ca2+ current at 0 mV with EC50 Of 5.4+/-0.94 mu mol/l and Hill coefficient of 1.1+/-0.14 (n=6). In addition, 10 mu mol/l fluoxetine shifted the midpoint of the steady-state inactivation curve of the Ca2+ current from -20.7+/-0.65 to -26.7+/-1 mV (P<0.001, n=8) without changing its slope factor. These effects of fluoxetine developed rapidly and were fully reversible. Fluoxetine did not alter voltage-dependence of activation or time constant for inactivation of I-Ca. Fluoxetine had no effect on the amplitude of K+ currents (I-K1 and I-to). The inhibition of cardiac Ca2+ and Na+ channels by fluoxetine may explain most cardiac side effects observed occasionally with the drug. Our results suggest that fluoxetine may have antiarrhythmic (class I + IV type), as well as proarrhythmic properties (due to impairment of atrioventricular or intraventricular conduction and shortening of repolarization). Therefore, in depressed patients with cardiac disorders, ECG control may be suggested during fluoxetine therapy.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Naunyn-Schmiedebergs Archives of Pharmacology. - 361 : 1 (2000), p. 67-73. -
További szerzők:Magyar János (1961-) (élettanász) Szigligeti Péter Bányász Tamás (1960-) (élettanász) Pankucsi Csaba (farmakológus) Korom Zsuzsanna Ungvári Zoltán Kecskeméti Valéria Nánási Péter Pál (1956-) (élettanász)
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8.

001-es BibID:BIBFORM030343
035-os BibID:WOS:A1995TG10200009 PMID:8751081
Első szerző:Pankucsi Csaba (farmakológus)
Cím:Electrophysiological effects of dridocainide on isolated canine, guinea-pig and human cardiac tissues / Csaba Pankucsi, Mária Hegedus, Anikó Kovacs, Gábor Szenasi, Katalin Szemeredi, Péter P. Nanasi
Dátum:1995
ISSN:0028-1298
Megjegyzések:The cellular electrophysiological effects of dridocainide (EGIS-3966), a novel class I antiarrhythmic agent, was studied using conventional microelectrode techniques in canine cardiac Purkinje fibres and papillary muscle preparations obtained from humans and guinea-pigs. In each preparation, dridocainide (0.6-2 mu mol/l) decreased the maximum velocity of action potential upstroke (V-max) in a frequency-dependent manner, although marked differences were observed in its effects in Purkinje fibre and ventricular muscle preparations. In canine Purkinje fibres, action potential duration measured at 50% and 90% of repolarization was decreased, while action potential duration measured at 10% of repolarization was increased by dridocainide. In addition, the plateau of the action potential was depressed by the drug. These changes in action potential configuration were not observed in guinea pig or human papillary muscles. The offset kinetics of the dridocainide-induced V-max block were different in Purkinje fibres and in ventricular muscle: the slow time constant of recovery of V-max was estimated to be 2.5 s in dog Purkinje fibre and 5-6 s in human and guinea-pig papillary muscle. In guinea-pig papillary muscle, the rate of onset of the V-max block was 0.15 and 0.2 per action potential in the presence of 0.6 and 2 mu mol/l dridocainide, respectively. Dridocainide also decreased the force of contraction in this preparation. On the basis of the present results, dridocainide appears to posess mixed class I.C and I.A properties, with I.C predominance in human and guinea-pig ventricular muscle. Present results also indicate that results of conventional classification of class I drugs may depend on the parameters chosen, as well as on the preparation selected.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Naunyn-Schmiedebergs Archives of Pharmacology. - 352 : 5 (1995), p. 520-528. -
További szerzők:Hegedűs Mária Kovács Anikó Szénási Gábor Szemeredi Katalin Nánási Péter Pál (1956-) (élettanász)
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9.

001-es BibID:BIBFORM030334
035-os BibID:18465595
Első szerző:Pankucsi Csaba (farmakológus)
Cím:Novel antiarrhythmic agents with combined mode of action / Csaba Pankucsi, János Magyar, Tamás Bányász, Péter Mátyus, Péter P. Nánási
Dátum:1998
ISSN:1369-7056 (Linking)
Megjegyzések:In spite of the accelerated evolution in antiarrhythmic drug research and design,the ideal antiarrhythmic compound has not yet emerged. Pure class III agents havenot been clinically successful, mainly due to their torsadogenic side-effects.Combination of class III effect with class I, II or IV effects has given bettertherapeutic results, whilst combination of the various antiarrhythmic mechanismswithin one molecule, rather than combination of drugs, seems to be an even morepromising strategy. In this study, we briefly review the most frequently appliedantiarrhythmic combinations, focusing primarily to those novel antiarrhythmicswhere class III effects are combined with class IV or class I actions within thesame single molecule.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:IDrugs : the investigational drugs journal. - 1 : 5 (1998), p. 554-60. -
További szerzők:Magyar János (1961-) (élettanász) Bányász Tamás (1960-) (élettanász) Mátyus Péter (1962-) (vegyész) Nánási Péter Pál (1956-) (élettanász)
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10.

001-es BibID:BIBFORM030279
Első szerző:Pankucsi Csaba (farmakológus)
Cím:Three distinct components of the negative inotropic action of lidocaine in dog Purkinje fiber / Csaba Pankucsi, András Varró, Péter P. Nánási
Dátum:1996
ISSN:0306-3623
Megjegyzések:1. The negative inotropic action of 10 mu M lidocaine and 100 mu M nicorandil was compared as a function of the pacing cycle length, ranging from 300-3000 ms, in isolated canine Purkinje fiber preparations. 2. The applied concentrations of lidocaine and nicorandil produced similar shortening of action potential duration; however, lidocaine compromised contractility stronger than nicorandil at each cycle length. 3. Normalizing the inotropic action of the drugs to their shortening effect on action potential duration, the negative inotropic action of lidocaine can be regarded as a sum of three distinct components: negative inotropy associated to the shortening of action potential duration per se, reduction of contractility likely due to direct inhibition of the fast sodium current and of the ''window'' sodium current by lidocaine.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:General Pharmacology. - 27 : 1 (1996), p. 69-71. -
További szerzők:Varró András (1954-) (farmakológus, klinikai farmakológus) Nánási Péter Pál (1956-) (élettanász)
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11.

001-es BibID:BIBFORM030278
035-os BibID:WOS:A1997WN91400013
Első szerző:Pankucsi Csaba (farmakológus)
Cím:Electrophysiological effects of EGIS-7229, a new antiarrhythmic agent, in isolated mammalian and human cardiac tissues / Csaba Pankucsi, Tamás Bányász, János Magyar, Ildikó Gyönös, Anikó Kovács, András Varró, Gábor Szénási, Péter P. Nánási
Dátum:1997
ISSN:0028-1298
Megjegyzések:The cellular electrophysiological effects of EGIS-7229 (5-chlor-4-[N-(3,4-dimethoxy-phenyl-ethyl)- amino-propylamino]-3(2H)-pyridazinone fumarate), a novel antiarrhythmic agent, was studied using conventional microelectrode techniques in canine cardiac Purkinje fibers and papillary muscle preparations obtained from man, rabbits and guinea pigs. Low concentration of EGIS-7229 (3 mu mol/l) selectively lengthened action potential duration (both APD(50) and APD(90)) in all preparations. The effect of higher concentrations (30-100 mu mol/l) of EGIS-7229 on action potential duration was variable depending on the preparation studied: in rabbit and human papillary muscles both APD(50) and APD(90) were lengthened, in canine Purkinje fibers APD(90) was lengthened but APD(50) was shortened, while in guinea pig papillary muscles both APD(50) and APD(90) were shortened by high concentrations of the drug. At these higher concentrations EGIS-7229 also decreased the maximum velocity of action potential upstroke (V-max) and depressed the plateau of action potentials without affecting the resting membrane potential or action potential amplitude. Both reduction of V-max and lengthening of APD were frequency dependent. The former effect was more prominent at higher pacing frequencies, while the latter was more pronounced at lower driving rates. In guinea pig papillary muscle, the time constant of recovery from V-max block was 719 +/- 33 ms (n = 18) and the rate of onset of the block was 1.81 +/- 0.06 AP(-1) (n = 16) in the presence of 100 mu mol/l EGIS-7229. EGIS-7229 had a complex action on refractoriness in guinea pig papillary muscles: ERP was lengthened at low concentrations (3 to 10 mu mol/l), unchanged at 30 mu mol/l and shortened at 100 mu mol/l. The ratio of ERP/APD(90) however, was significantly increased at concentrations higher than 3 mu mol/l. In canine Purkinje fiber when the delayed rectifier K current (I-K) was blocked by d-sotalol (60 mu mol/l) and APD was shortened back to its control value by additional application of nicorandil (15 mu mol/l), APD was not affected by 3 mu mol/l but was shortened by 30 mu mol/l of EGIS-7229. 100 mu mol/l EGIS-7229 shortened APD in guinea pig papillary muscle. This effect of EGIS-7229 was effectively prevented by nifedipine pretreatment (10 mu mol/l). In this preparation, EGIS-7229 also decreased the V-max of the slow action potential, evoked in the presence of 20 mmol/l external K+ plus 0.5 mmol/l Ba2+. It is likely that EGIS-7229 at low concentrations blocks I-K in human, canine, rabbit and guinea pig cardiac preparations, but at higher concentrations also inhibits Ca and Na currents. Therefore, EGIS-7229 appears to carry mixed class III, IV and IB antiarrhythmic properties.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Naunyn-Schmiedebergs Archives of Pharmacology. - 355 : 3 (1997), p. 398-405. -
További szerzők:Bányász Tamás (1960-) (élettanász) Magyar János (1961-) (élettanász) Gyönös Ildikó Kovács Anikó Varró András (1954-) (farmakológus, klinikai farmakológus) Szénási Gábor Nánási Péter Pál (1956-) (élettanász)
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001-es BibID:BIBFORM030277
035-os BibID:WOS:A1997XM42500024
Első szerző:Pankucsi Csaba (farmakológus)
Cím:Electrophysiological effects of EGIS-7229, a new antiarrhythmic agent, in isolated guinea pig papillary muscle / Csaba Pankucsi, Tamás Bányász, János Magyar, Ildikó Gyönös, Anikó Kovács, Gábor Szénási, András Varró, Péter P. Nánási
Dátum:1997
ISSN:0306-3623
Megjegyzések:1. The cellular electrophysiological effects of EGIS-7229, a novel antiarrhythmic agent, were studied in guinea pig papillary muscles with the use of conventional microelectrode techniques. 2. The drug had a concentration-dependent biphasic effect on action potential duration (APD). APD was significantly lengthened at low concentration (3 mu mol/l), whereas it was shortened at concentrations higher than 10 mu mol/l. 3. At concentrations higher than 10 mu mol/l, the drug decreased the maximum velocity of action potential upstroke (V-max), the force of contraction, and altered the restitution kinetics of APD. 4. The effect of EGIS-7229 on V-max was frequency dependent; it was most prominent at short pacing cycle lengths (use-dependent block). 5. On the basis of present results, EGIS-7229 appears to carry mixed class I and class III characteristics, Class III properties are present at low concentrations, whereas, at higher concentrations, class I actions may be predominant. GEN PHARMAC 29;2:275-280, 1997. (C) 1997 Elsevier Science Inc.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:General Pharmacology 29 : 2 (1997), p. 275-280. -
További szerzők:Bányász Tamás (1960-) (élettanász) Magyar János (1961-) (élettanász) Gyönös Ildikó Kovács Anikó Szénási Gábor Varró András (1954-) (farmakológus, klinikai farmakológus) Nánási Péter Pál (1956-) (élettanász)
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