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1.

001-es BibID:BIBFORM030359
035-os BibID:PMID:2036332 WOS:A1991FB89300003
Első szerző:Knilans, Timothy K.
Cím:Electrophysiologic effects of FPL 13210 on canine Purkinje fiber action potential duration and Vmax comparison to disopyramide / T. K. Knilans, A. Varro, P. P. Nanasi, R. J. Murray, F. C. Kaiser, D. A. Lathrop
Dátum:1991
ISSN:0920-3206
Megjegyzések:The frequency-dependent effects of FPL 13210, a new disopyramide derivative, were examined in isolated canine cardiac Purkinje fibers paced at a frequency of 2 Hz and following abrupt changes in pacing cycle length. At 2 Hz, FPL 13210 depressed V(max), while shortening action potential duration measured at 50% of repolarization (ADP50) and not affecting duration measured at 90% of repolarization (ADP90). These effects were concentration dependent over the range of 1-30-mu-M. The depression of V(max) produced by 5-mu-M FPL 13210 was not significantly different than that produced by 18-mu-M disopyramide while the preparations were paced constantly at 2 Hz. At these concentrations, recovery of V(max) was slowed by both FPL 13210 and disopyramide. The slow time constant estimated for this relation after exposure to FPL 13210 was approximately 6.5 times longer than that estimated following administration of disopyramide. In addition, APD90s evoked by early premature stimuli in the presence of 5-mu-M FPL 13210 were longer than those produced in the absence of drug when the diastolic interval was less than 60 ms. Later extra stimuli evoked at diastolic intervals longer than 100 ms produced shorter APD90s after FPL 13210 administration. Therefore, when FPL 13210 is compared to disopyramide using concentrations selected to produce equivalent degrees of V(max) depression, FPL 13210 produced effects on APD90 that were opposite to those produced by disopyramide when the diastolic interval was longer than normal. These effects of FPL 13210 would suggest that this compound should be classified as a class Ic antiarrhythmic agent, unlike disopyramide, a class Ia antiarrhythmic agent.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Cardiovascular Drugs and Therapy. - 5 : 1 (1991), p. 139-146. -
További szerzők:Varró András (1954-) (farmakológus, klinikai farmakológus) Nánási Péter Pál (1956-) (élettanász) Murray, R. J. Kaiser, F. C. Lathrop, David A.
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2.

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
Dátum:1991
ISSN:0007-1188
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
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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)
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3.

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
Dátum:1993
ISSN:0014-2999
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
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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)
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4.

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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5.

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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6.

001-es BibID:BIBFORM030282
Első szerző:Lathrop, David A.
Cím:In vitro cardiac models of dog Purkinje fibre triggered and spontaneous electrical activity : effects of nicorandil / David A. Lathrop, Péter P. Nánási, András Varró
Dátum:1990
ISSN:0007-1188
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:British Journal of Pharmacology. - 99 : 1 (1990), p. 119-123. -
További szerzők:Nánási Péter Pál (1956-) (élettanász) Varró András (1954-) (farmakológus, klinikai farmakológus)
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7.

001-es BibID:BIBFORM030499
035-os BibID:PMID:2279686 WOS:A1990EB78600008
Első szerző:Nánási Péter Pál (élettanász)
Cím:Different actions of aconitine and veratrum alkaloids on frog skeletal muscle / Péter P. Nanasi, Tamás Kiss, Miklós Danko, David A. Lathrop
Dátum:1990
ISSN:0306-3623
Megjegyzések:1. The electrophysiological effects of veratridine, cevadine and aconitine (10(-8)-2 x 10(-4), 2 x 10(-7)-2 x 10(-6) and 2 x 10(-6)-10(-4) mol/l, respectively) were compared on frog muscle membrane using conventional microelectrodes. 2. Veratridine and aconitine were equally effective in depolarizing the resting membrane with the threshold concentration of 5 x 10(-5) mol/l. 3. Volleys of repetitive discharges and slow transient depolarizations were observed when single electrical stimuli were applied in the presence of veratridine (5 x 10(-8)-2 x 10(-5) mol/l), but not aconitine. Volleys with aconitine could be evoked only by repetitive stimulation; however no tendency of repolarization was observed following these volleys. Two orders of magnitude more aconitine than veratridine was required to induce volleys with similar parameters. 4. The effects of cevadine were similar to those of the corresponding concentrations of veratridine. 5. The observed differences between the electrophysiological actions of aconitine and veratrum alkaloids may be explained in part with differences in Na+ channel inactivation produced by these toxins, in addition to differences in their use-dependent behavior.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:General Pharmacology. - 21 : 6 (1990), p. 863-868. -
További szerzők:Kiss Tamás Dankó Miklós Lathrop, David A.
Pályázati támogatás:2/666/88
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8.

001-es BibID:BIBFORM030354
035-os BibID:PMID:1330809 WOS:A1992HT47500003
Első szerző:Nánási Péter Pál (élettanász)
Cím:Nonlinear relationship between V+max and h infinity in frog skeletal muscle / P. P. Nanasi, M. Danko, A. Varro, D. A. Lathrop
Dátum:1992
ISSN:0231-5882
Megjegyzések:The relationship between the maximum velocity of action potential upstroke (V(max)+) and steady-state Na+ channel inactivation (h(infinity)) was studied in frog skeletal muscle during repetitive discharges evoked in the presence of cevadine (1-mu-mol/l). Conventional microelectrodes and vaseline-gap voltage-clamp techniques were used. A severe degree of nonlinearity was found between (h(infinity)) and (V(max)+) especially when the Na+ conductance (gNa) was small. The observed nonlinearity could be explained as a property of the normal Na+ channel gating in skeletal muscle rather than that of cevadine-modified channels. Part of this work has been published in abstract form in Biophys. J. 57: 105A, 1990.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:General Physiology and Biophysics. - 11 : 2 (1992), p. 159-167. -
További szerzők:Dankó Miklós Varró András (1954-) (farmakológus, klinikai farmakológus) Lathrop, David A.
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9.

001-es BibID:BIBFORM030353
035-os BibID:PMID:1379481 WOS:A1992HZ14800003
Első szerző:Nánási Péter Pál (élettanász)
Cím:Ionic currents in ventricular myocytes isolated from the heart of a patient with idiopathic cardiomyopathy / P. P. Nanasi, A. Varro, D. A. Lathrop
Dátum:1992
ISSN:1015-5007
Megjegyzések:Whole-cell configuration of the patch-clamp technique was applied to record ionic currents from human ventricular myocytes isolated from a cardiac transplant patient with idiopathic cardiomyopathy. Inward calcium current, transient outward current, and inward rectifier potassium current were recorded, while no discernible delayed rectifier potassium current was observed. Thus the currents that underlie electrical activity in human ventricular myocytes appear to resemble those reported earlier in canine and rabbit ventricular myocytes.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Cardioscience. - 3 : 2 (1992), p. 85-89. -
További szerzők:Varró András (1954-) (farmakológus, klinikai farmakológus) Lathrop, David A.
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10.

001-es BibID:BIBFORM030352
035-os BibID:PMID:1356876 WOS:A1992JF22300027
Első szerző:Nánási Péter Pál (élettanász)
Cím:Biphasic effect of tetraethylammonium on canine purkinje fibre action potential configuration / Péter P. Nanasi, Timothy K. Knilans, Ira S. Richards, András Varro, David A. Lathrop
Dátum:1992
ISSN:0306-3623
Megjegyzések:1. Using conventional microelectrode techniques a biphasic effect of tetraethylammonium (5 mmol/l) on the configuration of action potentials recorded from isolated canine Purkinje fibres: action potentials were first shortened (early effect) and then lengthened (late effect) by tetraethylammonium. 2. The early effect of tetraethylammonium also included lengthening of phase 1 duration and elevation of the plateau amplitude. These early effects reached steady-state within the first 3 min of superfusion and were readily reversed within 3 min of initiating washout of the drug. 3. The late effect (gradual lengthening of repolarisation during phase 3) failed to reach steady-state within the initial 60 min of superfusion and was not reversible. 4. The early effects of tetraethylammonium were more marked at slow driving rates and were not affected by blockade of alpha- and beta-adrenoceptors using 1-mu-mol/l phentolamine and 1-mu-mol/l propranolol. 5. The early effects of tetraethylammonium were mimicked by 4-aminopyridine (0.5 mmol/l), and in the presence of 4-aminopyridine tetraethylammonium failed to induce further changes in action potential morphology. 6. The early effects of tetraethylammonium may be due to inhibition of the transient outward current. 7. The rapid onset and reversibility of these early effects suggest that tetraethylammonium may act from outside the cell membrane.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:General Pharmacology. - 23 : 4 (1992), p. 733-738. -
További szerzők:Knilans, Timothy K. Richards, Ira S. Varró András (1954-) (farmakológus, klinikai farmakológus) Lathrop, David A.
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11.

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
Dátum:1992
ISSN:0901-9928
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.
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12.

001-es BibID:BIBFORM030350
035-os BibID:PMID:7688582 WOS:A1993LL68800009
Első szerző:Nánási Péter Pál (élettanász)
Cím:Isolation of human ventricular and atrial cardiomyocytes : technical note / P. P. Nanasi, A. Varro, D. A. Lathrop
Dátum:1993
ISSN:1015-5007
Megjegyzések:Techniques suitable for the isolation of human cardiac cells have previously been reported. However, there are difficulties concerning the reliability and reproducibility of the available methods. In the present study, a technique developed for the isolation of canine cardiocytes was successfully applied to allow isolation of human atrial and ventricular myocytes from small samples of myocardium. Application of this method allowed a direct comparison of the ionic currents recorded from human atrial and ventricular myocytes with those recorded from other mammalian preparations.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Cardioscience. - 4 : 2 (1993), p. 111-116. -
További szerzők:Varró András (1954-) (farmakológus, klinikai farmakológus) Lathrop, David A.
Pályázati támogatás:1453
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