Összesen 4 találat.


001-es BibID:BIBFORM030281
Első szerző:Knilans, Timothy K.
Cím:Rate and concentration-dependent effects of UK-68,798, a potent new class III antiarrhythmic, on canine Purkinje fibre action potential duration and Vmax / Timothy K. Knilans, David A. Lathrop, Peter P. Nanasi, Arnold Schwartz, Andras Varro
Megjegyzések:1 The frequency-dependent electrophysiological effects of UK-68,798 in concentrations of 1, 3, 10 and 30 nM were examined in isolated cardiac Purkinje fibres of the dog at both a number of constant rates of stimulation and following abrupt changes in pacing cycle length. 2 In all concentrations evaluated, UK-68,798 lengthened action potential duration in a concentration- and rate-dependent manner (e.g., at a cycle length = 500 ms, control APD90 = 234.0 +/- 3.3 ms, while after 10 nM UK-68,798, APD90 = 315.0 +/- 5.9 ms). 3 The duration of action potentials evoked following abrupt changes in pacing rate were also increased in a concentration-dependent manner at all diastolic intervals tested. 4 The fast and slow time constants for restitution of APD were not altered by UK-68,798. However, the amplitude terms for this relation were increased. 5 In addition, the maximum upstroke velocity (V(max)) was not significantly affected by exposure to UK-68,798 at any concentration or diastolic interval. The kinetics for recovery of V(max) were thus unaffected. 6 These findings are similar to those previously reported for recognized class III antiarrhythmic agents (e.g., bretylium, clofilium, and sotalol); however, UK-68,798 was 1,000 to 10,000 times more potent. 7 The combined potency and selectivity of this agent seem to make it an ideal tool for the investigation of cardiac potassium channels believed responsible for controlling the duration of the action potential. 8 This potent and highly selective compound may prove extremely useful in the control of cardiac arrhythmias.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:British Journal of Pharmacology. - 103 : 2 (1991), p. 1568-1572. -
További szerzők:Lathrop, David A. Nánási Péter Pál (1956-) (élettanász) Schwartz, Arnold Varró András (1954-) (farmakológus, klinikai farmakológus)
Internet cím:elektronikus változat
Intézményi repozitóriumban (DEA) tárolt változat


001-es BibID:BIBFORM030347
035-os BibID:WOS:A1993LV61600003 PMID:8243533
Első szerző:Lathrop, David A.
Cím:Ionic basis for OPC-8212-induced increase in action potential duration in isolated rabbit, guinea pig and human ventricular myocytes / David A. Lathrop, Péter P. Nanasi, Arnold Schwartz, András Varro
Megjegyzések:Changes in transmembrane ionic currents induced by OPC-8212 (3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-l-piperazinyl]-2(1H)-quinoline) , a recently introduced positive inotropic agent which lengthens cardiac action potential duration, were examined using whole-cell voltage-clamp techniques in single rabbit, guinea pig and human ventricular myocytes. In rabbit, OPC-8212 (12 mumol/l) significantly increased membrane action potential duration measured at 90% of repolarization by an average of 88 ms (from 462 +/- 25 to 550 +/- 35 ms, n = 4; P < 0.05). In rabbit this increase in duration was not associated with significant changes in either the inward rectifier or transient outward K+ currents. The magnitude of the secondary inward current evoked from a holding potential of -50 mV was significantly increased by 97 +/- 8% (n = 6; P < 0.01) while a demonstrable delayed rectifier outward current could not be identified in the rabbit myocytes examined at room temperature. In guinea pig ventricular myocytes, where the delayed rectifier was large, 12 mumol/l OPC-8212 significantly depressed the current by 58 +/- 10% (n = 6; P < 0.01). The effects of OPC-8212 in human ventricular myocytes obtained from the explanted heart of a single patient having an idiopathic cardiomyopathy most closely resembled those observed in isolated rabbit ventricular myocytes. Thus, in rabbit and a few human ventricular myocytes examined at room temperature, OPC-8212 appeared to lengthen cardiac membrane action potential duration primarily by increasing the amplitude of the secondary inward current believed to primarily represent current through L-type Ca2+ channels. In guinea pig preparations, OPC-8212 also decreased the delayed rectifier outward K+ current which also would account for an increase in action potential duration. OPC-8212 could not be demonstrated to affect Na+ current inactivation in a manner similar to that produced by 1 mg/l veratrine, a recognized Na + channel agonist, which dramatically slowed this process.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:European Journal of Pharmacology. - 240 : 2-3 (1993), p. 127-137. -
További szerzők:Nánási Péter Pál (1956-) (élettanász) Schwartz, Arnold Varró András (1954-) (farmakológus, klinikai farmakológus)
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat


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
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
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat


001-es BibID:BIBFORM030351
035-os BibID:PMID:1523194 WOS:A1992JH25000010
Első szerző:Nánási Péter Pál (élettanász)
Cím:Active and passive electrical properties of isolated canine cardiac Purkinje fibers under conditions simulating ischaemia : effect of diltiazem / Péter P. Nanasi, Timothy K. Knilans, András Varro, Anne M. Murphy, Akira Fujiki, Arnold Schwartz, David A. Lathrop
Megjegyzések:The effect of a calcium channel blocker diltiazem on the electrical properties of canine Purkinje fibers superfused in a milieu similar to that occurring in acute myocardial ischaemia was studied. Action potential parameters, passive electrical properties, and conduction velocity were measured using conventional microelectrode techniques. Superfusion with glucose-free Tyrode's solution containing 9 mM K+, gassed with 100% N2 at pH = 6.5 ('ischemic solution') significantly reduced the maximal diastolic potential, action potential duration, maximal upstroke velocity, conduction velocity and length constant, while input resistance and longitudinal resistance were elevated and membrane resistance remained unchanged. Diltiazem (1-mu-M) alone reduced only the action potential duration, while all other parameters were unaffected. Pretreatment with diltiazem did not fully prevent the effects of ischemic superfusion; however, the ischaemia-induced decrease in length constant was not significant in the presence of diltiazem. In addition, the increase in longitudinal resistance during ischaemia was significantly reduced following diltiazem pretreatment. This decrease in longitudinal resistance may contribute to the improvement of ischaemia-induced conduction delay observed in intact animals and may be related to a reduction of ischaemia-induced increase in intracellular free Ca2+.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Pharmacology & Toxicology. - 71 : 1 (1992), p. 52-56. -
További szerzők:Knilans, Timothy K. Varró András (1954-) (farmakológus, klinikai farmakológus) Murphy, Anne M. Fujiki Akira Schwartz, Arnold Lathrop, David A.
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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