Combined application of class I antiarrhythmic drugs causes "additive", "reductive", or "synergistic" sodium channel block in cardiac muscles

1990 ◽  
Vol 24 (11) ◽  
pp. 925-931 ◽  
Author(s):  
T. Kawamura ◽  
I. Kodama ◽  
J. Toyama ◽  
H. Hayashi ◽  
H. Saito ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Antiarrhythmic Drugs ◽  
Class I ◽  
Channel Block ◽  
Combined Application ◽  
Cardiac Muscles

scholarly journals Open and inactivated sodium channel block by class-I antiarrhythmic drugs

1986 ◽  
Vol 40 ◽  
pp. 138
Author(s):  
Itsuo Kodama ◽  
Junji Toyama ◽  
Kazuo Yamada
Keyword(s):  
Sodium Channel ◽  
Antiarrhythmic Drugs ◽  
Class I ◽  
Channel Block

Biochemical and biophysical studies of the interaction of class I antiarrhythmic drugs with the cardiac sodium channel

1994 ◽  
Vol 33 (3) ◽  
pp. 277-294 ◽  
Author(s):  
Gerald W. Zamponi ◽  
Henry J. Duff ◽  
Robert J. French ◽  
Robert S. Sheldon
Keyword(s):  
Sodium Channel ◽  
Antiarrhythmic Drugs ◽  
Class I ◽  
Cardiac Sodium Channel ◽  
Biophysical Studies

scholarly journals State-dependent PH-dependent binding of class I antiarrhythmic drugs to a receptor associated with sodium channel

1990 ◽  
Vol 15 (2) ◽  
pp. A41
Author(s):  
Mohammed Taouis ◽  
Roger J. Hill ◽  
Henry J. Duff ◽  
Leslie M. Wilson ◽  
Robert S. Sheldon
Keyword(s):  
Sodium Channel ◽  
Antiarrhythmic Drugs ◽  
Class I ◽  
State Dependent ◽  
Ph Dependent

Opposite change with ischaemia in the antifibrillatory effects of class I and class IV antiarrhythmic drugs resulting from the alteration in ion transmembrane exchanges related to depolarization

2000 ◽  
Vol 78 (3) ◽  
pp. 208-216 ◽  
Author(s):  
Jean-François Aupetit ◽  
Bernard Bui-Xuan ◽  
Idriss Kioueh ◽  
Joseph Loufoua ◽  
Dominique Frassati ◽  
...  
Keyword(s):  
Action Potential ◽  
Calcium Channel ◽  
Sodium Channel ◽  
Sodium Channels ◽  
Antiarrhythmic Drugs ◽  
Channel Blocker ◽  
Class I ◽  
Monophasic Action Potential ◽  
Channel Blockers ◽  
Class Iv

It is known that class I antiarrhythmic drugs lose their antifibrillatory activity with severe ischaemia, whereas class IV antiarrhythmic drugs acquire such activity. Tachycardia, which is also a depolarizing factor, has recently been shown to give rise to an alteration of ion transmembrane exchanges which is particularly marked in the case of calcium. This leads one to wonder if the change in antifibrillatory activity of antiarrhythmic drugs caused by ischaemia depends on the same process. The change in antifibrillatory activity was studied in normal conditions ranging to those of severe ischaemia with a class I antiarrhythmic drug, flecainide (1.00 mg·kg-1 plus 0.04 mg·kg-1·min-1), a sodium channel blocker, and a class IV antiarrhythmic drug, verapamil (50 µg·kg-1 plus 2 µg·kg-1·min-1), a calcium channel blocker. The experiments were performed in anaesthetized, open-chest pigs. The resulting blockade of each of these channels was assessed at the end of ischaemic periods of increasing duration (30, 60, 120, 180, 300, and 420 s) by determining the ventricular fibrillation threshold (VFT). VFT was determined by means of trains of diastolic stimuli of 100 ms duration delivered by a subepicardial electrode introduced into the myocardium (heart rate 180 beats per min). Ischaemia was induced by completely occluding the left anterior descending coronary artery. The monophasic action potential was recorded concurrently for the measurement of ventricular conduction time (VCT). The monophasic action potential duration (MAPD) varied with membrane polarization of the fibres. The blockade of sodium channels by flecainide, which normally raises VFT (7.0 ± 0.4 to 13.8 ± 0.8 mA, p < 0.001) and lengthens VCT (28 ± 3 to 44 ± 5 ms, p < 0.001), lost its effects in the course of ischaemia. This resulted in decreased counteraction of the ischaemia-induced fall of VFT and decreased aggravation of the ischaemia-induced lengthening of VCT. The blockade of calcium channels, which normally does not alter VFT (between 7.2 ± 0.6 and 8.4 ± 0.7 mA, n.s.) or VCT (between 30 ± 2 and 34 ± 3 ms, n.s.), slowed the ischaemia-induced fall of VFT. VFT required more time to reach 0 mA, thus delaying the onset of fibrillation. Membrane depolarization itself was opposed as the shortening of MAPD and the lengthening of VCT were also delayed. Consequently there is a progressive decrease in the role played by sodium channels during ischaemia in the rhythmic systolic depolarization of the ventricular fibres. This reduces or suppresses the ability of sodium channel blockers to act on excitability or conduction, and increases the role of calcium channel blockers in attenuating ischaemia-induced disorders.Key words: pigs, ion transmembrane exchanges, myocardial ischaemia, sodium channel, calcium channel.

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