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 antiarr hythmic effects. Methods and Results-Reentrant circuits in the epicardial border zone (EBZ) of healing canine infarcts were mapped during sustained ventricular tachyca rdia, The cardiac-specific L-type calcium current enhancer Bay Y5959 preven ted initiation of sustained ventricular tachycardia in 7 of 14 experiments. Bay Y5959 caused slowing of conduction in areas of slow nonuniform conduct ion in reentrant circuits; block eventually occurred. Conduction was not af fected 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 improv ed conduction of premature impulses so that lines of unidirectional block n ecessary for VT initiation were not formed, an effect not related to a chan ge in the effective refractory period at the site of block. Conclusions-Block of conduction caused by enhanced L-type calcium current i n 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.