Effect of ATP-Sensitive Potassium Channel Inhibition on Resting Coronary Vascular Responses in Humans

Abstract

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 μg/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 μg). 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 (PP=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 (PP=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.