In vitro cardiac models of dog Purkinje fibre triggered and spontaneous electrical activity: effects of nicorandil.
1. The effects of nicorandil (30 microM and 100 microM) on two models of triggered activity [early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs)] and on spontaneous automaticity occurring from both normal and depolarized levels of membrane potential were examined in isolated cardiac Purkinje fibres of the dog. Standard intracellular microelectrode techniques were used. 2. Nicorandil (30 microM) abolished EADs provoked by superfusion with Tyrode solution containing 2.7 mM K+ and 3 mM Cs. 3. DADs were induced by 0.2 microM acetylstrophanthidin in Tyrode solution containing 5.4 mM K+. Nicorandil (30 microM) significantly reduced the amplitude of these DADs from 12.5 +/- 2.5 mV to 5.5 +/- 0.2 mV (P less than 0.02, n = 6), while DADs were fully abolished by 100 microM nicorandil. 4. In unstimulated Purkinje strands, superfused with 2.7 mM K+ containing Tyrode solution having a pH of either 7.4 or 6.8, spontaneous depolarizations developed with a mean maximum diastolic potential (MDP) of -84.6 +/- 1.6 mV (n = 9) or -54.0 +/- 1.2 mV (n = 9), respectively. Nicorandil significantly reduced the frequency of this automatic activity and caused its cessation, at either level of MDP. Nicorandil, however, produced significant hyperpolarization only when automaticity occurred from the depolarized level of potential. 5. These results suggest that nicorandil may exert significant antiarrhythmic actions in vivo by abolishing both spontaneous and triggered electrical activity.
Lathrop
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DA
Department of Pediatrics, University of Cincinnati College of Medicine, Ohio.
Nànàsi
P P
PP
Varrò
A
A
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006329:Heart Conduction System / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology*
D009536:Niacinamide; D020108:Nicorandil