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001-es BibID:	BIBFORM030254
Első szerző:	Kovács Anikó
Cím:	Effects of EGIS-7229 (S 21407), a novel class III antiarrhythmic drug, on myocardial refractoriness to electrical stimulation in vivo and in vitro / Anikó Kovács, Ildikó Gyönös, János Magyar, Tamás Bányász, Péter P. Nánási, Michael Spedding, Gábor Szénási
Dátum:	2001
ISSN:	0160-2446
Megjegyzések:	The I-Kr blocker EGIS-7229 (S-21407), displays class Ib and class IV effects that may alter its pharmacologic profile compared with those of pure I-Kr blockers. Therefore, the concentration- and frequency-dependent effects of EGIS-7229, and of the I-Kr blockers d,l-sotalol and dofetilide, on the effective refractory period (ERP) were measured in isolated right ventricular papillary muscle of the rabbit in vitro. The effects of these drugs on right ventricular fibrillation threshold (RVFT) at increasing intravenous doses were also determined in anesthetized cats. Dofetilide and d,l-sotalol increased ERP in a concentration-dependent manner (dofetilide: 3-100 nM; d,l-sotalol: 3-100 muM) with strong reverse frequency dependence at high concentrations. EGIS-7229 concentration dependently lengthened ERP at 1-30 muM. Its effect on ERP was clearly reverse frequency dependent at 3 muM, but this feature of the drug diminished at 10 muM and was not apparent at 30 muM The effect of EGIS-7229 (30 muM) on ERP was devoid of reverse frequency dependence as it was more effective (31%) than dofetilide (16 %) at high-pacing rate (3 Hz), whereas it was less effective (50%) than dofetilide (70%) at slow-pacing rate (1 Hz). Reverse frequency-dependent ERP effect of dofetilide (100 nM) was similarly abolished by the addition of lidocaine (30 muM). EGIS-7229 (1-8 mg/kg iv), d,l-sotalol (1-8 mg/kg iv), and dofetilide (10-80 mug/kg iv) caused a dose-dependent increase in RVFT. The minimum effective dose of d,l-sotalol and EGIS-7229 was 1 and 2 mg/kg, respectively. whereas that of dofetilide was 10 mug/kg. EGIS-7229 induced a smaller peak effect in RVFT than sotalol or dofetilide. In conclusion, EGIS-7229 markedly increased refractoriness to electrical stimulation in vitro and in vivo. Compared with pure I-Kr blockers, the benefits of EGIS-7229 seem to be a greater lengthening of effective refractory period at rapid stimulation rates, suggesting a strong antiarrhythmic action, and a smaller effect at slow stimulation rates, suggesting low potential to induce early afterdepolarizations.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban egyetemen (Magyarországon) készült közlemény
Megjelenés:	Journal of Cardiovascular Pharmacology. - 37 : 1 (2001), p. 78-88. -
További szerzők:	Gyönös Ildikó Magyar János (1961-) (élettanász) Bányász Tamás (1960-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Spedding, Michael Szénási Gábor
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001-es BibID:	BIBFORM030342
035-os BibID:	10684410
Első szerző:	Lathrop, David A.
Cím:	Comparison of the electromechanical effects of vesnarinone and amrinone in isolated dog Purkinje strands and ventricular trabeculae / David A. Lathrop, Péter P. Nánási, András Varró, Arnold Schwartz
Dátum:	1996
ISSN:	1074-2484 (Linking)
Megjegyzések:	BACKGROUND: Conventional microelectrode techniques were used to compare theconcentration-dependent effects of vesnarinone (0.1-100 microM) and amrinone (1microM-1 mM) on action potential duration (APD) and developed force in bothisolated dog ventricular trabeculae and Purkinje strands. METHODS AND RESULTS:Both drugs increased contractility of trabecular muscle preparations, while, inPurkinje strands, vesnarinone failed to increase developed force duringcontinuous pacing at 2 Hz. Vesnarinone lengthened APD in both preparations;although this effect was more marked in Purkinje strands. Ventricular muscle APDwas not affected by amrinone (1 microM to 1 mM), while, in Purkinje strands,amrinone produced a biphasic effect on APD. Low concentrations (1-100 microM) ofamrinone shortened Purkinje fiber APD, while only the highest concentration (1mM) used lengthened APD. In addition, in Purkinje strand preparations the effectsof vesnarinone (10 microM) on APD and developed force were proportional to pacingcycle length at frequencies slower than 2 Hz; however, at frequencies faster than2 Hz vesnarinone decreased developed force while APD was lengthened. Inventricular trabecular muscle preparations, the effects of vesnarinone were notaffected by frequency. CONCLUSIONS: These results indicate clear differencesbetween the effects of vesnarinone and amrinone in isolated cardiac preparations.These differences in experimental effects in isolated cardiac preparations mayhelp provide an explanation for the disappointing clinical response of patientsin heart failure to amrinone, while vesnarinone has appeared to be beneficial.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban egyetemen (Magyarországon) készült közlemény
Megjelenés:	Journal of cardiovascular pharmacology and therapeutics. - 1 : 2 (1996), p. 133-140. -
További szerzők:	Nánási Péter Pál (1956-) (élettanász) Varró András (1954-) (farmakológus, klinikai farmakológus) Schwartz, Arnold
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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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