Mono-N-dealkyldisopyramide (MND), the major metabolite of disopyramide, reaches significant concentrations in patients; however, little is known about its electrophysiological effects. We therefore assessed its activity in canine ventricular tissue superfused in vitro. MND produced a concentration and rate dependent increase in the magnitude of V$ sb{ rm max}$ depression. MND shortened all phases of repolarization in Purkinje fibers but prolonged action potential duration and effective refractory period in ventricular muscle. / We then assessed the effects of the combination of disopyramide and MND at clinically relevant concentrations. The combination produced additive effects on depression of V$ sb{ rm max}.$ MND accentuated the shortening of action potential duration in Purkinje fibers and the prolongation of refractory periods in both Purkinje fibers and ventricular muscle produced by disopyramide at normal heart rates. / In contrast, at slow stimulation rates and under redisposing electrolyte conditions, disopyramide produced a reverse use-dependent prolongation of action potential duration which led to the development of early afterdepolarizations and triggered activity in Purkinje fibers. Mexiletine and pacing abolished triggered activity, while MND shifted the incidence of triggered activity to longer cycle lengths.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.59865 |
| Date | January 1990 |
| Creators | Toy, William |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Pharmacology & Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001116129, proquestno: AAIMM66507, Theses scanned by UMI/ProQuest. |
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