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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
külföldön készült közlemény
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
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
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3.

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.
Internet cím:DOI
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4.

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.
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
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5.

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.
Internet cím:DOI
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6.

001-es BibID:BIBFORM030535
035-os BibID:WOS:A1990EV73600012
Első szerző:Varró András (farmakológus, klinikai farmakológus)
Cím:Concentration- and rate-dependent electrophysiological effects of restacorin on isolated canine Purkinje fibres / András Varró, Timothy K. Knilans, Péter P. Nanasi, György Rabloczky, David A. Lathrop
Dátum:1990
ISSN:0028-1298
Megjegyzések:The cellular electrophysiological effects of restacorin, a new antiarrhythmic agent were studied using conventional microelectrode techniques in isolated dog cardiac Purkinje fibres. Restacorin (1-30 mumol/l) decreased the maximum rate of rise of the action potential upstroke and action potential amplitude while action potential duration measured at 90% of repolarization was shortened in a concentration-dependent manner during pacing at a constant basic cycle length of 500 ms. The effect of 10 mumol/l restacorin on maximal rate of rise of the action potential upstroke and on action potential duration measured at 90% of repolarization were also studied while varying the constant pacing cycle length between 300 and 5000 ms. The results of these studies indicated a rate-dependent effect of restacorin on the action potential characteristics examined. After abrupt changes in cycle length, 10 mumol/l restacorin slowed the fast component of the relation for restitution of action potential duration from 155.3 +/- 5.2 ms (control, n = 6) to 217.1 +/- 17.8 ms (n = 6, P less than 0.05). In the presence of restacorin (10 mumol/l), a second slow component for recovery of maximal action potential upstroke rising velocity was expressed having a time constants of 8.5 +/- 1.2 s. The range of premature action potential durations was significantly decreased (by 57.1%, P less than 0.01) by 10 mumol/l restacorin. These results indicate that the cellular electrophysiological effects produced by restacorin in dog cardiac Purkinje fibres best resemble those produced by recognized class Ic antiarrhythmic drugs.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Naunyn-Schmiedebergs Archives of Pharmacology. - 342 : 6 (1990), p. 691-697. -
További szerzők:Knilans, Timothy K. Nánási Péter Pál (1956-) (élettanász) Rablóczky György Lathrop, David A.
Internet cím:DOI
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