A K(ATP) channel opener inhibited myocardial reperfusion action potential shortening and arrhythmias.
Low concentrations of certain K(ATP) channel openers have been reported to exert a moderate inhibitory effect on arrhythmias during post-ischaemic early myocardial reperfusion, but the accompanying effects on the time course of changes in action potentials in intact hearts have not yet been studied. We report that in rat isolated hearts, reperfusion following 10 min of regional no-flow ischaemia was associated with both an acute, marked, but transient, shortening of ventricular repolarisation (by 63%) during reperfusion, and a high incidence (90%) of ventricular tachyarrhythmias. The K(ATP) channel opener Ro 31-6930 [2-(6-cyano-2,2-dimethyl-2H-1-benzopyran-4-yl)-pyridine 1-oxide], delivered prior to ischaemia at a relatively low concentration (0.5 microM), significantly reduced the incidence and duration of reperfusion arrhythmias, and prevented the associated acute action potential shortening during reperfusion, each in a glibenclamide (1 microM)-sensitive manner (P<0.05, n=10-15 hearts). This was associated with a moderate and non-arrhythmogenic action potential shortening during ischaemia (a potentially "cardioprotective" effect). However, these data highlight the potential harm these drugs may cause, since a higher concentration of Ro 31-6930 caused marked shortening of action potentials and significant pro-arrhythmia during ischaemia.
Workman
A J
AJ
Department of Pharmacology, School of Applied Sciences, De Montfort University, The Gateway, LE1 9BH, Leicester, UK. A.J.Workman@clinmed.gla.ac.uk
MacKenzie
I
I
Northover
B J
BJ
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000503:physiopathology; D001578:Benzopyrans / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D017202:Myocardial Ischemia / Q000503:physiopathology; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology*; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000959:Antihypertensive Agents; D001578:Benzopyrans; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D011725:Pyridines; C062764:Ro 31-6930; D000255:Adenosine Triphosphate; D005905:Glyburide