Mechanisms of triggered arrhythmias

January, Craig T.; Cadman, Christopher S.; Shorofsky, Stephen R.

doi:10.1097/00019501-199204000-00012

Cited by 7 publications

(4 citation statements)

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“…As indicated in previous reports (Cranefield and Aronson, 1988;January et al, 1992), DADs are low-frequency (around 4-5 Hz) and low-amplitude depolarizing oscillations in membrane voltage that are triggered by one or more preceding action potentials. Afterdepolarizations that arise either before or after complete repolarization of the action potential are named early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs), respectively.…”

Section: Discussionsupporting

confidence: 58%

Effects of Resibufogenin from Toad Venom on Isolated Purkinje Fibers

et al. 2000

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Chan su (dried toad venom) is a traditional Chinese medicine obtained from the skin venom gland of the toad. Chan su has long been used as a therapeutic agent in China and other Asian countries. Recent reports indicate that Chan su toxicity carries a high mortality rate in the United States. This study focused upon the cardiac electrophysiological and electro-toxicity effects of resibufogenin (RBG), one of the major components in Chan su. Action potentials of isolated sheep and canine heart Purkinje fibers were studied using glass microelectrode recording techniques. The results indicate that RBG significantly affected all parameters of transmembrane action potential, induced delayed after depolarization, and triggered arrhythmias in sheep and canine Purkinje fibers.

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Section: Discussionsupporting

confidence: 58%

Effects of Resibufogenin from Toad Venom on Isolated Purkinje Fibers

et al. 2000

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“…No early or delayed afterdepolarizations were observed in experiments with spontaneously beating Purkinje fibres, a preparation which is very sensitive to this type of arrhythmia. There is some evidence that links early afterdepolarizations to clinical arrhythmia from type torsade de pointes (see January et al 1992). With GE 58 this type of proarrhythmic activity was not found in spontaneously beating Purkinje fibres of the guinea pig.…”

Section: Discussionmentioning

confidence: 99%

Electrophysiological properties of the propafenone-analogue GE 68 (1-[3-(phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol) in isolated preparations and ventricular myocytes of guinea-pig hearts

Lemmens‐Gruber

Heistracher

1997

Naunyn-Schmiedeberg's Arch Pharmacol

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GE 68 ((Rac.)-1-[3-(Phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol hydrochloride) is structurally related to propafenone, and exerts negative inotropic and negative chronotropic effects similar to the parent drug, but lacks any beta-adrenoceptor blocking activity contrary to propafenone. Thus, the electrophysiological effects of GE 68 were studied in papillary muscles, left atria, Purkinje fibres, sinoatrial nodes and ventricular myocytes of the guinea-pig heart with the intracellular microelectrode technique and the patch-clamp technique in the cell-attached mode. The decrease of the maximum upstroke velocity (Vmax) by GE 68 (1 to 10 microM) was use- and frequency-dependent. Vmax recovered from the use-dependent block with a time constant of 4.1 +/- 0.6 s. In papillary muscles and Purkinje fibres action potential duration was shortened, while it was prolonged in left atria and sinoatrial nodes. Half-maximal steady-state inactivation of the sodium channels was shifted to more negative membrane potentials (control: -91.5 +/- 0.8 mV, 10 microM GE 68: -97.9 +/- 2.5 mV). The peak of the current-voltage relationship and the reversal potential were not changed by GE 68. The amplitude of the unitary current remained unaltered, while open state probability was decreased. The most striking effect of GE 68 was an increase of the number of sweeps without single channel openings (1 microM: 2fold, 10 microM: 6fold). GE 68 also caused a decrease of the mean open times, and an increase of the mean closed times in unmodified and pronase-modified sodium channels. Besides the lack of beta-adrenoceptor blocking activity, data present a faster recovery from the use-dependent block by GE 68 and a lower affinity to inactivated sodium channels compared to the reference drug propafenone, as well as differences in the effect on single channel kinetics.

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“…That MAP duration and overall shape reflect these characteristics of the cellular action potential is well established [57,58]. These complications have been recognized as serious limitations of the extrapolation of experimental data and the use of MAP recordings in the clinical setting [61]. These complications have been recognized as serious limitations of the extrapolation of experimental data and the use of MAP recordings in the clinical setting [61].…”

Section: Map Recordingsmentioning

confidence: 99%

Effects of pinacidil, verapamil, and heart rate on afterdepolarizations in the guinea-pig heart in vivo

Zaim

Pelleg

1996

Heart Vessels

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Recently, ionic current simulation in the Luo-Rudy model has elucidated putative mechanisms of afterdepolarizations under various experimental conditions. The present study was aimed at gaining insight into the differential mechanism of different types of afterdepolarizations in the guinea-pig heart in vivo. The effects of pharmacological and heart rate perturbations on early (EADs) and delayed (DADs) afterdepolarizations, induced by either digoxin, CsCl, or BayK 8644 were studied, using mid-myocardial left ventricular monophasic action potential (MAP) recordings. Digoxin insignificantly shortened sinus cycle length (SCL) and CsCl and BayK 8644 differentially prolonged SCL and MAP duration. Digoxin induced phase 3-EADs and DADs and CsCl or BayK 8644 induced phase 2- and phase 3-EADs. Pinacidil shortened MAP duration, suppressed almost all the phase 2-EADs and some of the phase 3-EADs, but not the DADs. In a few cases, DADs were manifested following the abolishment of phase 2-EADs by pinacidil, but this phenomenon did not occur in the presence of hexamethonium. Verapamil prolonged SCL, did not significantly affect phase 2-EADs, but suppressed almost all of the DADs, including those which appeared after pinacidil, and all but one of the phase 3-EADs. The effects of pinacidil and verapamil were independent of the mode of afterdepolarization induction. A pacing-induced heart rate increase, which shortened MAP duration, and vagal stimulation, which prolonged MAP duration, attenuated and enhanced phase 2-EADs, respectively. The amplitude of phase 3-EADs was inversely related to the heart rate. These data, taken together, are consistent with those obtained previously by others in a computer model and recent observations on CsCl-induced EADs in the guinea-pig Purkinje fibers in vitro which have indicated that the mechanism of phase 2-EADs is different from that of DADs and that late phase 3-EADs generated under conditions of Ca2+ overload and DADs share similar properties.

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Mechanisms of triggered arrhythmias

Cited by 7 publications

References 0 publications

Effects of Resibufogenin from Toad Venom on Isolated Purkinje Fibers

Effects of Resibufogenin from Toad Venom on Isolated Purkinje Fibers

Electrophysiological properties of the propafenone-analogue GE 68 (1-[3-(phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol) in isolated preparations and ventricular myocytes of guinea-pig hearts

Effects of pinacidil, verapamil, and heart rate on afterdepolarizations in the guinea-pig heart in vivo

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