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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:905.)
© 2004 American Heart Association, Inc.

Vascular Biology

Effect of ATP-Sensitive Potassium Channel Inhibition on Coronary Metabolic Vasodilation in Humans

H. M. Omar Farouque; Stephen G. Worthley; Ian T. Meredith

From the Cardiovascular Research Centre, Monash Medical Centre and Monash University, Melbourne, Australia.

Correspondence to Ian T. Meredith, Cardiovascular Research Centre, Monash Medical Centre, 246 Clayton Road, Clayton, Melbourne, Victoria, 3168, Australia. E-mail ian.meredith{at}med.monash.edu.au

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.

Methods and 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 µg/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.

Key Words: blood flow • ion channels • sulfonylurea • vasoconstriction • coronary circulation

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