In vitro cardiac models of dog Purkinje fibre triggered and spontaneous electrical activity: effects of nicorandil

• Published in: British journal of pharmacology Vol. 99; no. 1; pp. 119 - 123
• Main Authors: Lathrop, David A., Nànàsi, Pèter P., Varrò, Andràs
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-01-1990; Nature Publishing
• Subjects: Action Potentials - drug effects; Animals; Antiarythmic agents; Biological and medical sciences; Cardiovascular system; Dogs; Electrophysiology; Female; heart; Heart - drug effects; Heart - physiology; Heart Conduction System - physiology; Hydrogen-Ion Concentration; In Vitro Techniques; Male; Medical sciences; Membrane Potentials - drug effects; Niacinamide - analogs & derivatives; Niacinamide - pharmacology; Nicorandil; Pharmacology. Drug treatments; Purkinje Fibers - drug effects; Purkinje Fibers - physiology; Heart; Fissipedia; Animal model; Carnivora; Arrhythmia; Electrophysiology; Cardiovascular disease; Purkinje fiber; In vitro; Depolarization; Vertebrata; Mammalia; Animal; Membrane potential; Mechanism of action; Dog; Antiarrhythmia agent
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1990.tb14664.x

1
The effects of nicorandil (30 μm and 100 μm) 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 μm) abolished EADs provoked by superfusion with Tyrode solution containing 2.7 mm K+ and 3 mm Cs.
3
DADs were induced by 0.2 μm acetylstrophanthidin in Tyrode solution containing 5.4 mm K+. Nicorandil (30 μm) significantly reduced the amplitude of these DADs from 12.5 ± 2.5 mV to 5.5 ± 0.2 mV (P > 0.02, n = 6), while DADs were fully abolished by 100 μm 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.