Effects of drugs on ventricular fibrillation and ischaemic K+ loss in a model of ischaemia in perfused guinea-pig hearts in vitro.
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.
Gwilt
M
M
Bioscience II Department, ICI Pharmaceuticals, Macclesfield, Cheshire, UK.
Henderson
C G
CG
Orme
J
J
Rourke
J D
JD
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D052160:Benzothiazoles; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004195:Disease Models, Animal; D005913:Glipizide / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D011719:Pyrazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D013565:Sympatholytics / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000517:prevention & control*
D000889:Anti-Arrhythmia Agents; D052160:Benzothiazoles; D002121:Calcium Channel Blockers; D010880:Piperidines; D015221:Potassium Channels; D011719:Pyrazines; D011725:Pyridines; D013565:Sympatholytics; D013844:Thiazoles; C069454:UK 66914; C054551:R 56865; D015761:4-Aminopyridine; D011188:Potassium; D005905:Glyburide; D005913:Glipizide