title: Effects of pharmacological modulation of the ATP-sensitive potassium channels on the development of warm-up angina pectoris.
abstract: The aim of this study was to examine the effect of pharmacological modulation of the ATP-sensitive potassium channels in the development of warm-up angina pectoris. Thirty-one patients with stable angina pectoris, a positive exercise test and angiographically documented coronary artery disease underwent three exercise tests 90 min after receiving either glibenclamide 10.5 mg (an ATP-sensitive potassium channel blocker), pinacidil 25 mg (an ATP-sensitive potassium channel opener) or placebo in a blinded fashion. There was a 30-min recovery period between the first and the second test and 60 min between the second and the third test. The rate-pressure product at 1-mm ST-segment depression (ischemic threshold) and the maximum ST-segment depression (STD) adjusted to the highest rate-pressure product common to the three tests were analyzed. In the placebo group, there was a significant increase in the ischemic threshold during the second and third test and a significant decrease in the maximum adjusted STD during the second test which was lost during the third test. This apparent adaptation to exercise-induced ischemia was not seen in the glibenclamide-treated patients. In the pinacidil-treated patients, there was a paradoxical decrease in ischemic threshold during the second test with no change in maximum adjusted STD which tended to be lower than in the placebo-treated patients on each exercise test. This study confirms that the warm-up phenomenon can be induced during repeated exercise testing. The blockade of this phenomenon by glibenclamide suggests that the ATP-sensitive potassium channels may be involved in this potential protective mechanism. At the same time, the paradoxical response in the pinacidil-treated patients flags a warning that drugs acting on the sarcolemmal ATP-sensitive potassium channels may have a direct effect on the ST-segment that may interfere with the interpretation of the electrocardiogram.
authors.affiliation: Department of Cardiology, Bispebjerg Hospital, Copenhagen, Denmark. Lindhardt@dadlnet.dk
authors.forename: Tommi Bo
authors.initials: TB
authors.lastname: Lindhardt
authors.forename: Sadollah
authors.initials: S
authors.lastname: Abedini
authors.forename: Rikke Mørch
authors.initials: RM
authors.lastname: Olesen
authors.forename: Stig
authors.initials: S
authors.lastname: Haunsø
authors.forename: Niels
authors.initials: N
authors.lastname: Gadsbøll
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D020110:Pinacidil / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; D020110:Pinacidil; D000255:Adenosine Triphosphate; D005905:Glyburide