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Modification by hypoxia, hyperkalaemia and acidosis of the cardiac electrophysiological effects of a range of antiarrhythmic drugs
Author(s) -
Pacini D.J.,
BoachieAnsah G.,
Kane K.A.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14504.x
Subject(s) - disopyramide , purkinje fibers , repolarization , electrophysiology , verapamil , depolarization , propranolol , membrane potential , resting potential , medicine , chemistry , cardiac transient outward potassium current , pharmacology , anesthesia , endocrinology , calcium , patch clamp , biochemistry
1 The electrophysiological effects of a series of drugs with Class I antiarrhythmic activity were examined in sheep Purkinje fibres, superfused in vitro with either a normal or hypoxic, hyperkalaemic and acidotic physiological salt solution (PSS). 2 In normal sheep Purkinje fibres, lignocaine, disopyramide, nicainoprol and propranolol all significantly reduced action potential height and the maximum rate of depolarization of phase zero (MRD) and abbreviated the action potential, without modifying resting membrane potential (RMP). 3 Verapamil at the highest concentration studied, 8 μ m , significantly reduced MRD with an associated slight membrane depolarization and abbreviated action potential duration measured at 50% repolarization (APD 50 ). 4 Superfusion of sheep Purkinje fibres with a hypoxic, hyperkalaemic and acidotic PSS resulted in marked reductions in resting membrane potential, upstroke and duration of the action potential. 5 In the presence of modified PSS, lignocaine, propranolol and verapamil all reduced MRD to a greater extent than in normal PSS. The effects of nicainoprol on MRD were not affected whereas those of disopyramide were significantly attenuated. 6 Under simulated ischaemic conditions, lignocaine, propranolol and nicainoprol did not produce a concentration‐dependent reduction in action potential duration whereas disopyramide and verapamil, respectively, prolonged and abbreviated both APD 50 and APD90. 7 The Na + channel blocking actions of the different subtypes of Class I antiarrhythmic agents studied, as well as their effects on action potential duration, were modified differently by simulated ischaemia.