Cellular mechanisms for cardiac arrhythmias.

Hoffman, Brian F.; Rosen, M R

doi:10.1161/01.res.49.1.1

Cited by 335 publications

(79 citation statements)

References 114 publications

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“…Similar results have been previously described in rabbit atrial fibres (Matsuo, 1967) as well as in ventricular muscle (Auclair et al, 1969;Garcia de Jalon et al, 1978;Rodriguez & Tamargo, 1980) and Purkinje fibres (Rawling & Fozzard, 1979;Rodriguez & Tamargo, 1980;Weld & Bigger, 1980 (Alexander & Nino, 1968;Jefferson, 1975) or toxic doses of Imip (Raeder, Burckhardt, Neubauer, Walter & Gastpar, 1978). Cardiac arrhythmias may be produced by enhanced automaticity and/or depressed conduction velocity (Hoffman & Rosen, 1981). The present results demonstrate that Imip may suppress arrhythmias which may result from both mechanisms.…”

Section: Discussionmentioning

confidence: 55%

Electrophysiological effects of imipramine in non‐treated and in imipramine‐pretreated rat atrial fibres

Manzanares

Tamargo

1983

British J Pharmacology

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The effect of imipramine (Imip) in concentrations between 10−7M and 5 × 10−5M has been studied on rat atrial transmembrane potentials. In another group of experiments the effect of Imip was studied in atrial fibres from rats pretreated for 24 days with twice daily intraperitoneal injections of Imip 7.5 mg/kg or saline. In non‐treated atria Imip depressed action potential amplitude and Vmax, reduced the resting membrane potential and shifted the membrane responsiveness and recovery time curves downward and to the right. Imip also prolonged the action potential duration and the effective refractory period, lengthening the effective refractory period relative to action potential duration. Pretreatment with Imip decreased the resting membrane potential, amplitude and Vmax of the action potential and prolonged the effective refractory period. Further addition of Imip produced similar but more marked changes than in non‐treated animals. Imip suppressed the spontaneous atrial automaticity as well as the abnormal automaticity induced by BaCl2, aconitine, ouabain or isoprenaline. The drug produced a negative inotropic effect and depressed the amplitude of the slow contractions elicited by isoprenaline in K‐depolarized atria. It is concluded that even when the effects of Imip are similar to those of quinidine (group I of antiarrythmics), it also produces a reduction in Ca and K conductances.

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Section: Discussionmentioning

confidence: 55%

Electrophysiological effects of imipramine in non‐treated and in imipramine‐pretreated rat atrial fibres

Manzanares

Tamargo

1983

British J Pharmacology

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“…EADs have been induced in isolated cardiac tissues under a variety of mines,'3 reduced potassium concentrations,'4 reduced pH,51'6 low calcium concentrations, '7 hypoxia,'8 aconitine,'9 N-acetylprocainamide, 20 sotalol,21 and cesium chloride. 2 In contrast to delayed afterdepolarizations, EADs are increasingly likely to occur at slow rates of stimulation. 12 This characteristic of EADs, along with their tendency to occur more readily during conditions of prolonged repolarization, has led to the suggestion that EADs may induce bradycardia-dependent arrhythmias as well as arrhythmias associated with the long QT syndrome .…”

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confidence: 99%

Effects of pacing on triggered activity induced by early afterdepolarizations.

Damiano¹,

Rosen²

1984

Circulation

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250

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Early afterdepolarizations (EADs) are depolarizing potentials that occur during phase 2 or phase 3 of repolarization. They can induce triggered activity and have been proposed as a cause for arrhythmias in the heart in situ. To determine the response of EADs and triggered activity to interventions analogous to those used in the clinic for identifying arrhythmogenic mechanisms, we used a pacing protocol to study the response of EADs to sustained drive and extrastimuli. Cesium chloride (5 to 20 mM), which induces triggered arrhythmias in the intact dog, was used to induce EADs in isolated canine Purkinje fibers, and these were studied by microelectrode techniques. Cesium prolonged action potential duration and induced two types of EADs. At a potassium concentration of 4 mM, EADs occurred at membrane potentials of -3 to -30 mV. They were initiated 240 to 680 msec after the action potential upstroke and were 2 to 30 mV in amplitude. Their amplitude increased as drive cycle length increased, but their coupling interval to the action potential did not change with drive cycle length. These EADs did not induce triggered action potentials. At a potassium concentration of 2 mM, EADs usually occurred at higher membrane potentials (-50 to -70 mV) and longer coupling intervals (470 to 1360 msec) and were manifested as a delay.of phase 3 repolarization. These EADs induced triggered action potentials. When the triggered rhythms became sustained, premature stimuli either reset or terminated them, depending on the maximum diastolic potential. Termination occurred more frequently as the maximum diastolic potential increased. The extent of overdrive suppression induced by pacing for 15 sec to 3 min also increased as the maximum diastolic potential increased. In summary, cesium induced EADs at low or high membrane potentials. The former did not induce triggered activity, but the latter did. The triggered rhythms that occurred were similar to abnormal automatic mechanisms in their response to overdrive pacing and extrastimuli.

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“…The current is responsible for delayed afterdepolarizations and triggered activity (HOFFMAN and ROSEN, 1981). There is evidence that ryanodine acts on cardiac muscle apparently through a single mechanism, i.e., the inhibition of Ca2 + release from the SR (SuTKO and KENYON, 1983) by modulating the calcium release channels of cardiac SR membrane (ROUSSEAU et al, 1987) and that the drug does not affect the slow inward Ca2 + current (SUTKO and KENYON, 1983).…”

Section: Discussionmentioning

confidence: 99%

Two differential mechanisms of automaticity in diseased human atrial fibers.

et al. 1988

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The ionic mechanisms of automaticity in spontaneously active preparations (n = 38) from "diseased" human atria were investigated. The cycle length (CL) of the automatic action potential (AAP) ranged from 0.6 to 4.5 s (mean + S.D.: 2.0 + 1.0 s). The AAP from preparations obtained from non-digitalized patients (group 1, n = 29) showed various CLs, in that 16 patients had a CL longer than 2.0 s (slow-type AAP) while in tissues from the other 13 patients, the CL was 2.0 s or less (fast-type AAP). On the other hand, all preparations obtained from the digitalized patients prior to cardiac surgery (group 2, n = 9) had the fast-type AAP (CL <_ 2.0 s). The slow-type AAP was accelerated and changed to the fast one after application of ouabain (1 µM) or by perfusing with 50% [Na + ]o Tyrode solution. Ryanodine (1 tiM), a specific inhibitor of calcium release from the sarcoplasmic reticulum (SR), markedly lengthened the CL of fast-type AAP, without affecting the slow-type AAP. In contrast, caffeine (15 mM) shortened the CL of the slow-type AAP and remarkably lengthened the CL of the fast-type AAP, as is the case in ryanodine. The rate of slow-type AAP was enhanced with an increase in [Ca2+]o and depressed with a decrease in [Ca2 +]o or with application of diltiazem, a Ca2 + channel blocker. The slow-type AAP was changed to the fast-type AAP by stretching the preparation by about 20%. In vitro preparations excised from patients with dilated atria revealed a shorter CL of AAPs. We conclude that in "diseased" human atrial preparations, the ionic mechanism responsible for generation of slow-and fast-type automaticity differs. Slow automaticity (CL >2.0 s) perhaps relates to activation of the slow inward Ca2 + current, while the fast-type automaticity (CL <2.0 s) is linked to cyclic increases in [Ca2 +]~.

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Cellular mechanisms for cardiac arrhythmias.

Cited by 335 publications

References 114 publications

Electrophysiological effects of imipramine in non‐treated and in imipramine‐pretreated rat atrial fibres

Electrophysiological effects of imipramine in non‐treated and in imipramine‐pretreated rat atrial fibres

Effects of pacing on triggered activity induced by early afterdepolarizations.

Two differential mechanisms of automaticity in diseased human atrial fibers.

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