Glibenclamide, but not class III drugs, prevents ischaemic shortening of the refractory period in guinea-pig hearts.
The effective refractory period was measured in paced (4 Hz) perfused guinea-pig hearts in vitro. The effective refractory period was linearly correlated with temperature of the perfusing solution: as temperature was reduced the effective refractory period was increased. Reduction of the coronary flow rate to 10% of control resulted in a marked reduction in the effective refractory period. UK-66,914, dofetilide, ibutilide and phentolamine caused a prolongation in the effective refractory period, but during ischaemia the effective refractory period was reduced by the same degree as in vehicle-treated hearts. Glibenclamide had no effect on the effective refractory period prior to ischemia but it abolished the ischaemia-induced shortening. These results suggest that the opening of KATP channels may be responsible for the ischaemia-induced shortening of the effective refractory period in perfused guinea-pig hearts and that the class III effects of UK-66,914, dofetilide and ibutilide are attenuated during ischaemia.
Tweedie
D
D
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, UK.
Henderson
C
C
Kane
K
K
D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects*; D005905:Glyburide / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D010627:Phenethylamines / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology; D013696:Temperature
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D011719:Pyrazines; D011725:Pyridines; D013449:Sulfonamides; C069454:UK 66914; C067192:ibutilide; C063533:dofetilide; D005905:Glyburide; D010646:Phentolamine