Effect of ATP-sensitive potassium channel inhibition on coronary metabolic vasodilation in humans.
OBJECTIVE
Experimental evidence indicates that ATP-sensitive potassium (K(ATP)) channels regulate coronary blood flow (CBF). However, their contribution to human coronary metabolic vasodilation is unknown.


RESULTS
Seventeen patients (12 male, age 58+/-10 years) were studied. Coronary hemodynamics were assessed before and after K(ATP) channel inhibition with subselective intracoronary glibenclamide infused at 40 microg/min in an angiographically smooth coronary artery after successful percutaneous coronary intervention to another vessel. Metabolic vasodilation was induced by 2 minutes of rapid right ventricular pacing. Coronary blood velocity was measured with a Doppler guidewire and CBF calculated. The time course of hyperemia was recorded for 2 minutes after pacing, and hyperemic volume was estimated from the area under the flow-versus-time curve (AUC). Compared with vehicle infusion (0.9% saline), glibenclamide reduced resting CBF by 9% (P=0.04) and increased resting coronary vascular resistance (CVR) by 15% (P=0.03). Glibenclamide reduced pacing-induced peak CBF (50.8+/-6.8 versus 42.0+/-5.4 mL/min, P=0.001), peak CBF corrected for baseline flow (25.1+/-4.6 versus 17.6+/-3.1 mL/min, P=0.01), and increased minimum CVR (2.6+/-0.3 versus 3.1+/-0.3 mm Hg/mL per minute, P=0.002). Compared with vehicle, glibenclamide reduced total AUC at 2 minutes (3535+/-397 versus 3027+/-326 mL, P=0.001).


CONCLUSIONS
Vascular K(ATP) channels appear to be involved in functional coronary hyperemia after metabolic stimulation.
Farouque
H M Omar
HM
Cardiovascular Research Centre, Monash Medical Centre and Monash University, Melbourne, Australia.
Worthley
Stephen G
SG
Meredith
Ian T
IT
D000255:Adenosine Triphosphate / Q000502:physiology; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D006328:Cardiac Catheterization; D002304:Cardiac Pacing, Artificial; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000378:metabolism / Q000628:therapy; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006801:Humans; D006940:Hyperemia / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011955:Receptors, Drug / Q000187:drug effects* / Q000502:physiology; D015203:Reproducibility of Results; D014664:Vasodilation / Q000187:drug effects*
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011955:Receptors, Drug; C067662:glibenclamide receptor; D000255:Adenosine Triphosphate; D011188:Potassium; D005905:Glyburide