The antiarrhythmic efficacy of intravenous anipamil against occlusion and reperfusion arrhythmias.
1. Anipamil, a long acting analogue of verapamil, was tested for its actions against arrhythmias induced by ischaemia and reperfusion in conscious and anaesthetized rats, as well as for effects on epicardial intracellular action potentials. 2. When given 15 min or 4 h before coronary occlusion, 1 and 5 mg kg-1 anipamil reduced ischaemia-induced arrhythmias in conscious rats. The same doses also reduced arrhythmias when given 15 min before occlusion in acutely-prepared anaesthetized rats. ED50 values were between 1 and 5 mg kg-1. 3. The incidence of reperfusion arrhythmias depended upon the period of regional ischaemia prior to reperfusion such that the peak incidence occurred after 5-7 min of ischaemia. Anipamil (2.5 mg kg-1, i.v.) selectively abolished the reperfusion arrhythmias induced by short periods of ischaemia, although some antiarrhythmic effects were seen for all periods of ischaemia. 4. Anipamil slowed the rate of development of R-wave increases and S-T segment elevations induced by ischaemia, but did not reduce the maximum values they attained. 5. Anipamil (2.5 mg kg-1 i.v.) lacked Class I or III electrophysiological actions on intracellular action potentials recorded in vivo from the epicardium of rat hearts. 6. In conclusion, the antiarrhythmic actions of anipamil appeared to depend upon calcium antagonism which may have reduced arrhythmias by a combination of anti-ischaemic and direct anti-arrhythmic actions. Presumed anti-ischaemic actions changed the relationship between the duration of preceding ischaemia and resulting reperfusion arrhythmias.
MacLeod
B A
BA
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Moult
M
M
Saint
K M
KM
Walker
M J
MJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D003327:Coronary Disease / Q000503:physiopathology; D003331:Coronary Vessels / Q000502:physiology*; D004562:Electrocardiography; D004594:Electrophysiology; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D011437:Propylamines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D015427:Reperfusion Injury / Q000503:physiopathology*
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D011437:Propylamines; C045313:anipamil