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Does mexiletine reduce the maximal rate of rise of the action potential and conduction velocity in isolated papillary muscles of guinea pigs?
Does mexiletine reduce the maximal rate of rise of the action potential and conduction velocity in isolated papillary muscles of guinea pigs?
Mexiletine depresses the maximal rate of rise of the action potential and conduction velocity, suggesting its antiarrhythmic effects are most prominent in damaged cardiac cells with reduced resting potentials.
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May guide understanding of class Ib effects in depolarized tissue; leaves open clinical translation pending human studies.
Summary We studied the effects of the antiarrhythmic compound mexiletine on the maximal rate of rise (JOURNAL/jcph/04.03/00005344-198203000-00011/OV0312/v/2021-02-06T190229Z/r/image-pngmax) of the action potential and on conduction velocity in isolated papillary muscles of guinea pigs. Action potentials and JOURNAL/jcph/04.03/00005344-198203000-00011/OV0312/v/2021-02-06T190229Z/r/image-pngmax were measured by means of conventional microelectrodes. The conduction velocity was determined from extracellular recordings. Mexiletine (concentrations, 4.6 × 10−5 and 1.15 × 10−4 mol/L) caused a depression of JOURNAL/jcph/04.03/00005344-198203000-00011/OV0312/v/2021-02-06T190229Z/r/image-pngmax that depended on the condition examined. The hx curve relating JOURNAL/jcph/04.03/00005344-198203000-00011/OV0312/v/2021-02-06T190229Z/r/image-pngmax of the action potential to the resting membrane potential was shifted along the voltage axis to more negative membrane potentials. Qualitatively equal effects were observed on the curve of membrane responsiveness relating JOURNAL/jcph/04.03/00005344-198203000-00011/OV0312/v/2021-02-06T190229Z/r/image-pngmax to the membrane potential during the phase of repolarization of the preceding action potential. Eventually, marked prolongation of the recovery kinetics of JOURNAL/jcph/04.03/00005344-198203000-00011/OV0312/v/2021-02-06T190229Z/r/image-pngmax by mexiletine, as well as frequency-dependent reduction of JOURNAL/jcph/04.03/00005344-198203000-00011/OV0312/v/2021-02-06T190229Z/r/image-pngmax, could be demonstrated. The action of mexiletine on conduction velocity was very similar to its influence on JOURNAL/jcph/04.03/00005344-198203000-00011/OV0312/v/2021-02-06T190229Z/r/image-pngmax. Thus, a prolongation of the recovery kinetics was found of about the same magnitude as that measured in JOURNAL/jcph/04.03/00005344-198203000-00011/OV0312/v/2021-02-06T190229Z/r/image-pngmax. Similarly, in experiments with K+-induced depolarizations, a dependence on the membrane potential of the action of mexiletine on the conduction velocity could be demonstrated. The results suggest that mexiletine may exert antiarrhythmic effects mainly in damaged cardiac cells exhibiting a moderately reduced resting potential.
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Hohnloser et al. (1982) studied this question.
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