Comparison of antiarrhythmic and electrophysiologic effects of diltiazem and its analogue siratiazem.
We compared the abilities of diltiazem and siratiazem to protect the heart against coronary artery occlusion and reperfusion-induced arrhythmias in anaesthetised rats and assessed their effects on cardiac action potentials (APs) recorded in paced sheep Purkinje fibres. Both drugs in the concentration range of 0.5-4 mg kg-1 reduced the number of ventricular ectopic beats and the percentage of incidence of ventricular tachycardia (VT) that occurred during the first 7 min after coronary artery occlusion. The incidence of ventricular fibrillation (VF) on reperfusion was significantly reduced by siratiazem at a concentration of 2 mg kg-1 only. These antiarrhythmic effects were not accompanied by a reduction in mortality but were associated with a marked and sustained bradycardia and a decrease in mean arterial blood pressure (MAP). In sheep Purkinje fibres, diltiazem and siratiazem (10(-6)-10(-5) M) caused concentration-dependent reductions in AP duration measured at both 50 and 90% of repolarisation (APD50 and APD90), in the maximum rate of depolarisation of phase 0 and in AP amplitude (APA). Resting membrane potential (RMP) was not modified by either drug. The antiarrhythmic effects of both diltiazem and siratiazem may be due in part to direct electrophysiologic effects on cardiac tissue to block sodium and calcium channels and in part to an antiischaemic effect associated with bradycardia and vasodepression.
Guc
M O
MO
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland.
Boachie-Ansah
G
G
Kane
K A
KA
Wadsworth
R M
RM
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003327:Coronary Disease / Q000517:prevention & control*; D004110:Diltiazem / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004558:Electric Stimulation; D004594:Electrophysiology; D006321:Heart / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D011690:Purkinje Fibers / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control; D012756:Sheep
D000889:Anti-Arrhythmia Agents; C085176:siratiazem; D004110:Diltiazem