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SELECTIVE DEPRESSION OF MAXIMUM RATE OF DEPOLARIZATION OF GUINEA‐PIG VENTRICULAR ACTION POTENTIALS BY AMIODARONE AND LIGNOCAINE IN SIMULATED ISCHAEMIA: COMPARISON WITH ENCAINIDE
Author(s) -
Campbell Terence J.,
Hemsworth Paul D.
Publication year - 1990
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1990.tb01296.x
Subject(s) - amiodarone , depolarization , anesthesia , sodium channel blocker , resting potential , medicine , chemistry , antiarrhythmic agent , cardiology , pharmacology , sodium channel , sodium , heart disease , organic chemistry , atrial fibrillation
SUMMARY 1. Standard microelectrode techniques were used to record intracellular action potentials from guinea‐pig ventricular myocardium superfused with either control physiological saline (pH 7.5; p O 2 500 mmHg; [K+] 5.6 mmol/L) or ‘simulated ischaemic’ solution (pH 6.4; p O 2 90 mmHg; [K+] 11.2 mmol/L). 2. The effects on action potential parameters of therapeutic concentrations of lignocaine, amiodarone and encainide were studied under both conditions. 3. Simulated ischaemia, in the absence of drugs, produced marked reductions in resting potential (‐ 86.6 ± 2.3 to ‐ 64.7 ± 3.5 mV), maximum rate of depolarization (V̇ max ; 263 ± 66 to 106 ± 36 V/s) and action potential duration (164 ± 24 to 97 ± 26 ms). No drug produced any additional effect on resting potential. 4. All three drugs produced enhanced depression of V max in ischaemia compared to control conditions (class I effect). This was much more marked for lignocaine and amiodarone (inactivated channel blockers) than for encainide (open channel blocker). 5. In addition the prolongation of action potential duration seen with acute exposure to amiodarone (174 ± 12 to 192 ± 17 ms; class III effect) was abolished under simulated ischaemic conditions. 6. It is concluded that lignocaine and amiodarone exert greater selectivity for ischaemic tissue than does encainide and that amiodarone may function primarily as a class I agent under ischaemic conditions.