Effects of altered extracellular potassium and pacing cycle length on the class III antiarrhythmic actions of dofetilide (UK-68,798) in guinea-pig ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1992-08

AUTHORS

Tao Yang, Pål M. Tande, David A. Lathrop, Helge Refsum

ABSTRACT

The effects of altered extracellular K+ concentrations ([K+]0) and pacing cycle lengths (CLs) on the electrophysiological actions of dofetilide (UK-68,798), a potent class III antiarrhythmic agent, were examined in isolated guineapig ventricular papillary muscle. At a normal [K+]0 (4 mM) and at CL between 300 and 5000 msec, dofetilide (10 nM) significantly increased the action-potential duration (APD) and the effective refractory period (ERP), whereas other action-potential parameters were unaffected. Elevation of [K+]0 to 10 mM reduced membrane diastolic potential (MDP), action-potential amplitude (APA), and the maximum rising velocity of the action-potential upstroke (Vmax). These changes were accompanied by a small shortening of APD90, but with an increase in ERP; i.e., the ERP/APD90 ratio was increased. Dofetilide also significantly lengthened APD90 at 10 mM [K+]0 and at each CL. Even at the short cycle lengths (300 and 500 msec), dofetilide-induced increases in APD90 were not attenuated whether [K+]0 was at 4 or 10 mM. These results indicate that at various pacing CLs, 10 nM dofetilide increases myocardial APD and ERP to a similar extent without significant reverse use-dependence when the cell membrane is normally polarized or partially depolarized by elevated [K+]0. Dofetilide may, therefore, be expected to be beneficial in the treatment of cardiac tachyarrhythmias related or unrelated to regional myocardial hyperkalemia during myocardial ischemia. More... »

PAGES

429-436

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/bf00054193

DOI

http://dx.doi.org/10.1007/bf00054193

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1053012116

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/1520650


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