uk-66914 and Disease-Models--Animal

In a perfused guinea-pig heart model of myocardial ischaemia, reducing coronary flow by 95% for four successive 6 min periods caused a reproducible net loss of K+ into the coronary perfusate. This was reduced in a concentration-dependent manner by ATP dependent K+ channel blockers (glibenclamide and glipizide) and calcium channel blockers (verapamil and nifedipine). Other K+ channel blockers (UK-66,914, 4-aminopyridine, R56865 and phentolamine) and beta 1-adrenoceptor and beta 2-adrenoceptor antagonists (betaxolol and ICI118551) did not reduce this loss significantly. A single 30 min low-flow period reliably induced K+ release and ventricular fibrillation in control hearts. Glibenclamide, glipizide and phentolamine suppressed ventricular fibrillation but not ischaemic K+ loss in this model. R56865 and 4-aminopyridine and coadministration of betaxolol and ICI118551 yielded similar results while UK-66,914 suppressed neither. In our model, modulation of ischemic K+ loss and suppression of ventricular fibrillation were not closely associated and appeared to occur via separate mechanisms.

Topics: 4-Aminopyridine; Animals; Anti-Arrhythmia Agents; Benzothiazoles; Calcium Channel Blockers; Disease Models, Animal; Glipizide; Glyburide; Guinea Pigs; In Vitro Techniques; Male; Myocardial Ischemia; Piperidines; Potassium; Potassium Channels; Pyrazines; Pyridines; Sympatholytics; Thiazoles; Ventricular Fibrillation