Abstract:
:We examined the electromechanical effects of two class III antiarrhythmic agents, dofetilide (UK-68,798) and D-sotalol, in acidic myocardium. Right ventricular papillary muscle preparations isolated from guinea pigs were divided into three groups (n = 6 per group): (a) drug-free, (b) dofetilide (10 nM), and (c) D-sotalol (30 microM). At normal extracellular pH (pH = 7.32 +/- 0.01), dofetilide and D-sotalol lengthened action potential duration (APD) to a similar extent, i.e., by 18-20%. Effective refractory period (ERP) increased in parallel, whereas membrane diastolic potential (MDP), action potential amplitude (APA), maximum velocity of depolarization (Vmax), and developed force (DF) were not significantly affected. Metabolic acidosis (pH = 6.78 +/- 0.01) was simulated by reducing the bicarbonate concentration of the Tyrode's solution from 20 to 6 mM. Superfusion with acidic solution alone for 30 min markedly decreased Vmax and DF, whereas APD and ERP were lengthened slightly. The acidosis-induced decreases in Vmax and DF were not affected by pretreatment with dofetilide or D-sotalol. In acidic superfusate, both agents still significantly increased APD and ERP to the same extent that they did at normal pH. The results indicate that metabolic acidosis, a major component of myocardial ischemia, does not attenuate the class III antiarrhythmic action of dofetilide and D-sotalol.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Yang T,Tande PM,Refsum Hdoi
10.1097/00005344-199212000-00007subject
Has Abstractpub_date
1992-12-01 00:00:00pages
889-94issue
6eissn
0160-2446issn
1533-4023journal_volume
20pub_type
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journal_title:Journal of cardiovascular pharmacology
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