Dantrolene Sodium‐Induced Purkinje Fiber Action Potential Duration Prolongation and Its Relation to the Geometry of the Preparation

Abstract

Dantrolene‐Induced Purkinje Fiber Action Potential Prolongation. Introduction: The purpose of this study was to investigate the influence that the mode of drug administration and preparation geometry exerted on the ability of dantrolene to prolong sheep and canine Purkinje fiber (PF) action potential duration (APD). Methods and Results: Sheep PF with attached muscle were superfused with dantrolene 3–5 μg/mL for 90 minutes (group A), while identical preparations were incubated in dantrolene 33.3 μg/mL for 5 minutes, then washed for 60 minutes (group B). Additional preparations were incubated with dantrolene (as in group B) for 5 minutes, then washed for 60 minutes: sheep PF (group C); sheep PF attached to muscle at one end but tied off from the muscle (group D); PF as in group D with a freshly cut branch (group E); freshly cut canine PF (group F); and sheep PF attached to muscle at one end were placed in a partitioned bath and each side incubated with dantrolene separately and then washed for 60 minutes (group G). Superfusion (group A) or incubation (group B) with dantrolene prolonged PF APD by 93% and 83%, respectively (NS). Sealed PF of groups C and D: APD prolonged by 10% and 34%, respectively (compared to A, P < 0.01). Freshly cut PF in groups E and F: APD lengthened by 78% and 74%, respectively (compared to A, NS). Dantrolene administration to the PF side and to the muscle side in group G prolonged the PF APD on either side similarly. Conclusion: Thus, dantrolene is effective by prolonged superfusion or short incubation. Dantrolene penetrates sealed PF poorly, but readily penetrates freshly cut PF or ventricular muscle. In vitro geometry greatly influences dantrolene's effect on Purkinje fibers. (J Cardiovasc Electrophysiol, Vol. 3, pp. 119–127, April 1992)