Effects of verapamil and nifedipine on mechanisms of arrhythmia in an in vitro model of ischemia and reperfusion.
The effects of verapamil and nifedipine on cellular mechanisms of arrhythmia were examined in isolated canine Purkinje fiber-papillary muscles. Microelectrode recordings were made simultaneously from both tissues. Preparations were superfused with Tyrode's solution modified to mimic specific conditions of ischemia for 40 min with or without calcium channel blockers. Verapamil or nifedipine resulted in significantly greater depolarization of Purkinje tissue in response to ischemic conditions and increased the incidence of inexcitability or conduction block in Purkinje and muscle tissues. These calcium channel blockers caused only minor changes in ischemia-induced depolarization of muscle. In Purkinje tissue, return to nonischemic conditions in the absence of drugs caused, in sequence, oscillatory afterpotentials, temporary depolarization to inexcitability, and a phase of automaticity at low membrane potential. These events did not occur in muscle. Verapamil or nifedipine abolished oscillatory afterpotentials and low membrane potential automaticity in Purkinje tissue. However, reperfusion-induced depolarization and inexcitability of Purkinje tissue was delayed but not attenuated. This study demonstrates that verapamil or nifedipine exacerbate depolarization and depression of conduction in Purkinje tissue exposed to ischemic conditions. However, verapamil and nifedipine suppress some but not all potential mechanisms of arrhythmia induced by reperfusion.
Mohabir
R
R
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Ferrier
G R
GR
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D004594:Electrophysiology; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014700:Verapamil; D009543:Nifedipine