Effect of ATP-sensitive potassium channel inhibition on resting coronary vascular responses in humans.
Experimental data suggest that vascular ATP-sensitive potassium (K(ATP)) channels regulate coronary blood flow (CBF), but their role in regulating human CBF is unclear. We sought to determine the contribution of K(ATP) channels to resting conduit vessel and microvascular function in the human coronary circulation. Twenty-five patients (19 male/6 female, aged 56 +/- 12 years) were recruited. Systemic and coronary hemodynamics were assessed in 20 patients before and after K(ATP) channel inhibition with graded intracoronary glibenclamide infusions (4, 16, and 40 microg/min), in an angiographically smooth or mildly stenosed coronary artery following successful elective percutaneous coronary intervention to another vessel. Coronary blood velocity was measured with a Doppler guidewire and CBF calculated. Adenosine-induced hyperemia was determined following bolus intracoronary adenosine injection (24 microg). Time control studies were undertaken in 5 patients. Compared with vehicle infusion (0.9% saline), glibenclamide reduced resting conduit vessel diameter from 2.5 +/- 0.1 to 2.3 +/- 0.1 mm (P<0.01), resting CBF by 17% (P=0.05), and resting CBF corrected for rate pressure-product by 18% (P=0.01) in a dose-dependent manner. A corresponding 24% increase in coronary vascular resistance was noted at the highest dose (P<0.01). No alteration to resting CBF was noted in the time control studies. Glibenclamide reduced peak adenosine-induced hyperemia (P=0.01) but did not alter coronary flow reserve. Plasma insulin increased from 5.6 +/- 1.2 to 7.6 +/- 1.3 mU/L (P=0.02); however, plasma glucose was unchanged. Vascular K(ATP) channels are involved in the maintenance of basal coronary tone but may not be essential to adenosine-induced coronary hyperemia in humans.
Farouque
H M Omar
HM
Centre for Heart and Chest Research, Monash Medical Centre and Monash University, Melbourne, Australia.
Worthley
Stephen G
SG
Meredith
Ian T
IT
Skyrme-Jones
R Andrew P
RA
Zhang
Michael J
MJ
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D001783:Blood Flow Velocity / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000150:complications / Q000378:metabolism*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D005905:Glyburide / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D007261:Infusions, Intra-Arterial; D007328:Insulin / Q000097:blood; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D014654:Vascular Patency / Q000187:drug effects
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D000241:Adenosine; D005905:Glyburide