Document Detail


IK independent class III actions of MS-551 compared with sematilide and dofetilide during reperfusion in anaesthetized rats.
MedLine Citation:
PMID:  8922743     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. The antiarrhythmic and haemodynamic effects of three class III antiarrhythmic drugs, MS-551, sematilide and dofetilide, were examined in the coronary artery, ligation-reperfusion model of pentobarbitone-anaesthetized rats, a species deficient in functional cardiac IK. MS-551 is a non-selective potassium channel blocker, while both sematilide and dofetilide are selective delayed rectifier potassium (K) channel (IK) blockers. 2. Before coronary ligation, 3 and 10 mg kg-1 MS-551 decreased the heart rate by 6% (P < 0.01) and 12% (P < 0.01), and increased mean arterial pressure (MAP) by 14% (P < 0.05) and 33% (P < 0.01), respectively. Sematilide at 10 and 30 mg kg-1 also decreased the heart rate by 4% (P < 0.01) and 9% (P < 0.01), respectively, and the higher dose of 30 mg kg-1 decreased MAP by 29% (P < 0.01). Dofetilide, 1 mg kg-1, decreased the heart rate (P < 0.01), but had no significant effect on MAP. 3. The QT interval was increased by 10% (P < 0.01) and 31% (P < 0.01), when 3 and 10 mg kg-1 MS-551 were given. Sematilide and dofetilide had no effect on the QT interval. 4. Immediately after reperfusion, lethal ventricular fibrillation (VF) was induced in 80% of the saline group. MS-551 at 3 and 10 mg kg-1, reduced the incidence of lethal VF to 50% and 20% (P < 0.05). Neither dofetilide 1 mg kg-1 nor sematilide (10 and 30 mg kg-1) decreased the incidence of lethal VF (70%, 80% and 50%, respectively). None of the three drugs had any effect on the occurrence of reperfusion-induced VT or the total incidence of VF. However, 10 mg kg-1 MS-551 delayed the onset of reperfusion-induced VF (27 +/- 5 s compared with 12 +/- 2 s of the control group, P < 0.05). 5. In conclusion, in rats which are deficient in cardiac IK MS-551 prolonged the QT interval and reduced the incidence of sustained VF after reperfusion. Blockade of channels other than IK might participate in the defibrillatory effect of MS-551. Sematilide and dofetilide, which are selective IK blockers, did not increase the QT interval nor did they show antiarrhythmic effects Mechanisms other than K channel block may be involved in the different effects of the three drugs on blood pressure.
Authors:
J Chen; S Komori; B Li; K Tamura; K Hashimoto
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  British journal of pharmacology     Volume:  119     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1996 Nov 
Date Detail:
Created Date:  1997-03-10     Completed Date:  1997-03-10     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  937-42     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Yamanashi Medical University, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Arrhythmia Agents / pharmacology*
Blood Pressure / drug effects
Coronary Vessels / pathology
Heart Rate / drug effects
Ischemia
Male
Phenethylamines / pharmacology*
Procainamide / analogs & derivatives*,  pharmacology
Pyrimidinones / pharmacology*
Rats
Rats, Sprague-Dawley
Reperfusion
Sulfonamides / pharmacology*
Chemical
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Phenethylamines; 0/Pyrimidinones; 0/Sulfonamides; 101526-62-9/sematilide; 115256-11-6/dofetilide; 130656-51-8/MS 551; 51-06-9/Procainamide
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