ISSN:
1432-1912
Keywords:
Key words Dispersion
;
Refractoriness
;
ATP-sensitive potassium channel
;
Canine
;
Programmed electrical stimulation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The proarrhythmic effects of the ATP-sensitive potassium channel modulators cromakalim (n=10; 0.01 to 0.3 mg/kg i.v.), glibenclamide (n=10; 0.3 to 10 mg/kg i.v.) or volume equivalents of vehicle (n=10) were evaluated in post-infarcted anaesthetised dogs. Dogs were anaesthetised, subjected to an anterior-apical myocardial infarction, and allowed to recover. At 7.4±0.7 days post infarction, animals were anaesthetised again, electrophysiologic measurements (effective refractory periods, QT-intervals and ventricular fibrillation thresholds) were taken, and animals were tested for arrhythmias using a programmed electrical stimulation protocol. Only animals that did not have programmed electrical stimulation-inducible arrhythmias were used. Ventricular fibrillation thresholds were determined twice, once before the first dose then after the last dose of drug. At the end of the experiment, animals were subjected to ligation of the left circumflex coronary artery and survival was measured over the next two hours. Cromakalim significantly increased heart rate and decreased blood pressure. Although cromakalim significantly reduced effective refractory periods, it neither increased electrical dispersion, as determined by the standard deviation or coefficient of variance of the effective refractory period, nor did it enhance inducibility (0 out of 10 in both vehicle and cromakalim treated animals), change ventricular fibrillation thresholds, or reduce sudden death survival relative to vehicle. Glibenclamide did not increase electrical dispersion, but slightly increased the incidence of programmed electrical stimulation-induced arrhythmias (3 out of 10), and lowered ventricular fibrillation thresholds values. However, these changes were not statistically significant. Glibenclamide did not significantly affect survival relative to vehicle. Infarct sizes of the left ventricle were not statistically different among groups. In conclusion, cromakalim and glibenclamide did not affect dispersion of refractoriness. Glibenclamide did demonstrate a propensity towards proarrhythmic activity. However, the doses needed to observe proarrhythmic activity with glibenclamide were significantly higher than those needed for clinical treatment of hyperglycemia.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00176778
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