Electrophysiological effects of encainide and its metabolites in normal canine Purkinje fibers and Purkinje fibers surviving infarction

1989 ◽  
Vol 67 (7) ◽  
pp. 751-756
Author(s):  
Anne A. A. Kinnaird ◽  
Ricky Y. K. Man
Keyword(s):  
Myocardial Ischemia ◽  
Action Potential ◽  
Action Potential Duration ◽  
Refractory Period ◽  
Active Metabolite ◽  
Cardiac Action Potential ◽  
Purkinje Fibers ◽  
Cardiac Action ◽  
Electrophysiological Effects ◽  
Membrane Responsiveness

In this study, we assessed the effects of O-demethyl encainide (0.5 μM), the most active metabolite of encainide, and the combination with 3-methoxy-O-demethyl encainide (0.5 μM) and encainide (0.1 μM) on cardiac action potential characteristics in normal canine Purkinje fibers and Purkinje fibers surviving 24 h of myocardial ischemia. O-demethyl encainide decreased [Formula: see text] and conduction in normal Purkinje fibers and Purkinje fibers surviving infarction. Further decreases were observed with the combination. Action potential duration at both 50 and 95% repolarization was decreased by O-demethyl encainide. The combination of O-demethyl encainide, 3-methoxy-O-demethyl encainide, and encainide had no further effect. The combination of O-demethyl encainide, 3-methoxy-O-demethyl encainide, and encainide produced a smaller change in effective refractory period than O-demethyl encainide in normal Purkinje fibers and in Purkinje fibers surviving infarction. O-demethyl encainide and the combination shifted the membrane responsiveness curve to more negative potentials in both normal Purkinje fibers and Purkinje fibers surviving infarction. It is apparent from this study that there are differences in the effects of O-demethyl encainide and the combination of O-demethyl encainide, 3-methoxy-O-demethyl encainide, and encainide in normal Purkinje fibers compared with Purkinje fibers surviving infarction. Also, the combination used in this study had different electrophysiological effects than those of O-demethyl encainide alone.Key words: encainide, metabolites, electrophysiological effects, Purkinje fibers, infarction.

scholarly journals Beat-to-beat variability of cardiac action potential duration: underlying mechanism and clinical implications

2017 ◽  
Vol 95 (10) ◽  
pp. 1230-1235 ◽  
Author(s):  
Péter P. Nánási ◽  
János Magyar ◽  
András Varró ◽  
Balázs Ördög
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Feedback Regulation ◽  
Underlying Mechanism ◽  
Cardiac Action Potential ◽  
Clinical Implications ◽  
Cell Coupling ◽  
Negative Feedback Regulation ◽  
Cardiac Action ◽  
Cardiac Action Potential Duration

Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by ICa, IKr, and IKs while increased by INa, suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.

Frequency- and voltage-dependent effects of disopyramide in canine Purkinje fibers

1989 ◽  
Vol 67 (7) ◽  
pp. 710-721 ◽  
Author(s):  
Matthew A. Flemming ◽  
Betty I. Sasyniuk
Keyword(s):  
Potassium Channels ◽  
Action Potential ◽  
Sodium Channel ◽  
Action Potential Duration ◽  
Refractory Period ◽  
Drug Effect ◽  
Effective Refractory Period ◽  
Slow Inactivation ◽  
Purkinje Fibers ◽  
Rate Dependent

The voltage- and frequency-dependent blocking actions of disopyramide were assessed in canine Purkinje fibers within the framework of concentrations, membrane potentials, and heart rates which have relevance to the therapeutic actions of this drug. [Formula: see text] was used to assess the magnitude of sodium channel block. Disopyramide produced a concentration- and rate-dependent increase in the magnitude and kinetics of [Formula: see text] depression. Effects on activation time (used as an estimate of drug effect on conduction) were exactly analogous to effects on [Formula: see text]. A concentration-dependent increase in tonic block was also observed. Despite significant increases in tonic block at more depolarized potentials, rate-dependent block increased only marginally with membrane potential over the range of potentials in which propagated action potentials occur. Increases in extracellular potassium concentration accentuated drug effect on [Formula: see text] but attenuated drug effect on action potential duration. Recovery from rate-dependent block followed two exponential processes with time constants of 689 ± 535 ms and 15.7 ± 2.7 s. The latter component represents dissociation of drug from its binding site and the former probably represents recovery from slow inactivation. A concentration-dependent increase in the amplitude of the first component suggested that disopyramide may promote slow inactivation. There was less than 5% recovery from block during intervals equivalent to clinical diastole. Thus, depression of beats of all degrees of prematurity was similar to that of basic drive beats. Prolongation of action potential duration by therapeutic concentrations of drug following a long quiescent interval was minimal. However, profound lengthening of action potential duration occurred following washout of drug effect at a time when [Formula: see text] depression had reverted to normal, suggesting that binding of disopyramide to potassium channels may not be readily reversed. Variable effects on action potential duration may thus be attributed to a block of the window current flowing during the action potential being partially or over balanced by block of potassium channels. Purkinje fiber refractoriness was prolonged in a frequency-dependent manner. Disopyramide did not significantly alter the effective refractory period of basic beats but did increase the effective refractory period of sequential tightly coupled extra stimuli. The results can account for the antiarrhythmic actions of disopyramide during a rapid tachycardia and prevention of its initiation by programmed electrical stimulation.Key words: action potential duration, effective refractory period, upstroke velocity, conduction, rate of sodium channel unblocking.

scholarly journals Cardiac action potential duration and contractility in the intact dog heart.

1983 ◽  
Vol 345 (1) ◽  
pp. 75-85 ◽  
Author(s):  
A J Drake-Holland ◽  
M I Noble ◽  
M Pieterse ◽  
V J Schouten ◽  
W A Seed ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Cardiac Action Potential ◽  
Dog Heart ◽  
Cardiac Action ◽  
Cardiac Action Potential Duration

Detection of takeoff potential from intracellular recordings

1982 ◽  
Vol 242 (6) ◽  
pp. H1115-H1117
Author(s):  
R. McGillivray ◽  
R. W. Wald
Keyword(s):  
Electrical Stimulation ◽  
Membrane Potential ◽  
Action Potential ◽  
Cardiac Action Potential ◽  
Intracellular Recordings ◽  
Purkinje Fibers ◽  
Cardiac Action ◽  
Cardiac Purkinje Fibers ◽  
Cardioactive Drugs

The measurement of takeoff potential from intracellular recordings of the cardiac action potential may be useful in the study of the cardiac action potential may be useful in the study of spontaneous automaticity and of the effects of cardioactive drugs on active propagation. We describe a circuit capable of detecting and storing the membrane potential at a point where the slope of the membrane potential exceeds a preset value. The capability of this circuit to track the takeoff potential was tested using intracellular recordings from cardiac Purkinje fibers during spontaneous automaticity as well as during electrical stimulation.

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