Effect of ATP-sensitive potassium channel inhibition on coronary metabolic vasodilation in humans

Abstract

<h4>Objective</h4>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.<h4>Methods and results</h4>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).<h4>Conclusions</h4>Vascular K(ATP) channels appear to be involved in functional coronary hyperemia after metabolic stimulation.