New mechanism of antiarrhythmic drug action: increasing L-type calcium current prevents reentrant ventricular tachycardia in the infarcted canine heart.
BACKGROUND
We studied whether increasing L-type calcium current has antiarrhythmic effects.


RESULTS
Reentrant circuits in the epicardial border zone (EBZ) of healing canine infarcts were mapped during sustained ventricular tachycardia. The cardiac-specific L-type calcium current enhancer Bay Y5959 prevented initiation of sustained ventricular tachycardia in 7 of 14 experiments. Bay Y5959 caused slowing of conduction in areas of slow nonuniform conduction in reentrant circuits; block eventually occurred. Conduction was not affected in other regions of the circuits or in more normal areas of the EBZ, nor was the EBZ effective refractory period changed. Bay Y5959 also improved conduction of premature impulses so that lines of unidirectional block necessary for VT initiation were not formed, an effect not related to a change in the effective refractory period at the site of block.


CONCLUSIONS
Block of conduction caused by enhanced L-type calcium current in reentrant circuits may result from a decreased gap junctional conductance consequent to an increase in intracellular calcium. An increase in L-type calcium current may improve conduction of premature impulses.
Cabo
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Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
Schmitt
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Wit
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D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000502:physiology; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology*; D010496:Pericardium / Q000187:drug effects / Q000503:physiopathology; D013611:Tachycardia, Atrioventricular Nodal Reentry / Q000517:prevention & control*
D000889:Anti-Arrhythmia Agents; C109289:BAY y 5959; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines