Relevance of inter- and intraventricular electrical dispersion to arrhythmogenesis in normal and ischaemic rabbit myocardium: a study with cromakalim, 5-hydroxydecanoate and glibenclamide.
This study aimed to investigate the role of electrical dispersion in arrhythmogenesis by using K(ATP) channel modulating agents. Monophasic action-potential duration (MAPD90), effective refractory period (ERP), and conduction delay were measured at three ventricular sites in isolated working rabbit hearts. Cromakalim (10 microM), glibenclamide (3 microM), or 5-hydroxydecanoate (100 microM) were administered before and throughout 30 min of regional ischaemia and 15 min of reperfusion. Before ischaemia, cromakalim reduced MAPD90 and ERP in all areas and facilitated induction of ventricular fibrillation in five of 12 hearts. In these hearts, cromakalim increased interventricular ERP dispersion from 17 +/- 5 to 38 +/- 5 ms. During ischaemia, cromakalim decreased MAPD90 dispersion within the left ventricle from 84 +/- 5 to 44 +/- 4 ms, but did not affect ERP dispersion and arrhythmogenesis. 5-Hydroxydecanoate had no effect on MAPD90 and ERP shortening or dispersion during ischaemia and reperfusion and was not antiarrhythmic. Glibenclamide reduced forward flow to zero, preventing further electrophysiologic studies. In conclusion, in this model, an increase in interventricular ERP dispersion predisposes to ventricular fibrillation in normoxic conditions after cromakalim administration. However, a decrease in ischaemia-induced MAPD90 dispersion by cromakalim does not affect arrhythmogenesis. A lack of effect of 5-hydroxydecanoate on electrical dispersion during ischaemia is accompanied by a lack of antiarrhythmic activity.
Department of Medical Cardiology, Royal Infirmary, Glasgow, Scotland.
R
R
Wolk
S M
SM
Cobbe
K A
KA
Kane
M N
MN
Hicks
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000473:pathology*; D003327:Coronary Disease; D019806:Cromakalim / Q000494:pharmacology*; D003652:Decanoic Acids / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D006880:Hydroxy Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000473:pathology*; D015221:Potassium Channels / Q000187:drug effects*; D011817:Rabbits; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D014693:Ventricular Fibrillation / Q000473:pathology
D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D015221:Potassium Channels; D019806:Cromakalim; C052853:5-hydroxydecanoic acid; D005905:Glyburide