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001-es BibID:BIBFORM049713
Első szerző:Drimba László (farmakológus)
Cím:In Vivo Preclinical Evaluation of a Promising Antiarrhythmic Agent, EGIS-7229 / László Drimba, Jozsef Nemeth, Réka Sári, Yin Di, Anikó Kovács, Gábor Szénási, Zoltán Szilvássy, Barna Peitl
Dátum:2013
ISSN:0272-4391
Megjegyzések:The basic hemodynamic, electrophysiological, and pharmacological effects of EGIS-7229(E-7229) were evaluated and compared with those of a pure "Class III" antiarrhythmic drug (GLG-V-13) inconscious rabbits. Both compounds decreased heart rate dose-dependently. Mean arterial blood pressurewas not influenced by E-7229; however, GLG-V-13 produced a significant elevation on this parameter. Leftventricular end-diastolic pressure was gradually increased by E-7229, while GLG-V-13 induced moreconsiderable elevation on that at intermediate doses. QT and QTcb were lengthened by both compounds;however, higher doses of E-7229 resulted in shortening of the prolonged QT and QTcb.Ventricular effectiverefractory period (VERP) was significantly prolonged by either drug studied. Threshold doses to produceQT50%, QTmax, VERP50%, and VERPmax were significantly higher for E-7229 compared with GLG-V-13.Significantly higher doses were required for E-7229 to induce arrhythmias. The safety ratio was comparablefor both of the compounds. E-7229 can exert multiple actions on cardiac ion channels with minimalinfluence on hemodynamic parameters and reduced proarrhytmic profile in our preclinical model.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
cardiac arrhythmias
preclinical drug development
cardiovascular safety
preclinical model
Megjelenés:Drug Developmet Research. - 74 : 3 (2013), p. 173-185. -
További szerzők:Németh József (1954-) (vegyész, analitikus) Sári Réka (farmakológus) Di, Yin Kovács Anikó Szénási Gábor Szilvássy Zoltán (1957-) (belgyógyász, farmakológus, klinikai farmakológus) Peitl Barna (1972-) (orvos, farmakológus)
Pályázati támogatás:75965
OTKA
WNR7OS
WNR7OS
Internet cím:DOI
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2.

001-es BibID:BIBFORM042841
035-os BibID:PMID:23474828
Első szerző:Drimba László (farmakológus)
Cím:The role of acute hyperinsulinemia in the development of cardiac arrhythmias / László Drimba, Róbert Döbrönte, Csaba Hegedüs, Réka Sári, Yin Di, Joseph Németh, Zoltán Szilvássy, Barna Peitl
Dátum:2013
Megjegyzések:Patients with perturbed metabolic control are more prone to develop cardiac rhythm disturbances. The main purpose of the present preclinical study was to investigate the possible role of euglycemic hyperinsulinemia in development of cardiac arrhythmias. Euglycemic hyperinsulinemia was induced in conscious rabbits equipped with a right ventricular pacemaker electrode catheter by hyperinsulinemic euglycemic glucose clamp (HEGC) applying two different rates of insulin infusion (5 and 10 mIU/kg/min) and variable rate of glucose infusion to maintain euglycemia (5.5±0.5 mmol/l). The effect of hyperinsulinemia on cardiac electrophysiological parameters was continuously monitored by means of 12-lead surface ECG recording. Arrhythmia incidence was determined by means of programmed electrical stimulation (PES). The possible role of adrenergic activation was investigated by determination of plasma catecholamine levels and intravenous administration of a beta adrenergic blocking agent, metoprolol. All of the measurements were performed during the steady-state period of HEGC and subsequent to metoprolol administration. Both 5 and 10 mIU/kg/min insulin infusion prolonged significantly QTend, QTc, and Tpeak-Tend intervals. The incidence of ventricular arrhythmias generated by PES was increased significantly by euglycemic hyperinsulinemia and exhibited linear relationship to plasma levels of insulin. No alteration on plasma catecholamine levels could be observed; however, metoprolol treatment restored the prolonged QTend, QTc, and Tpeak-Tend intervals and significantly reduced the hyperinsulinemia-induced increase of arrhythmia incidence. Euglycemic hyperinsulinemia can exert proarrhythmic effect presumably due to the enhancement of transmural dispersion of repolarization. Metoprolol treatment may be of benefit in hyperinsulinemia associated with increased incidence of cardiac arrhythmias.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Naunyn-Schmiedeberg's Archives of Pharmacology. - 386 : 5 (2013), p. 435-444. -
További szerzők:Döbrönte Róbert Hegedűs Csaba (1983-) (Molekuláris biológus, Cera-Med Kft. Debrecen) Sári Réka (farmakológus) Di, Yin Németh József (1954-) (vegyész, analitikus) Szilvássy Zoltán (1957-) (belgyógyász, farmakológus, klinikai farmakológus) Peitl Barna (1972-) (orvos, farmakológus)
Pályázati támogatás:GOP-1.2.1-08-2009-0023
Egyéb
NKFP_07-A2-2008-0260
Egyéb
GOP-1.1.2-07/1-2008-0004
Egyéb
TÁMOP-4.2.2.-08/1-2008-0014
TÁMOP
OM-00174/2008
Egyéb
TÁMOP-4.2.2/B-10/1-2010-0024
TÁMOP
GOP-1.1.1-07/1- 2008-0032
Egyéb
OTKA-75965
OTKA
Internet cím:DOI
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