Published online before print December 13, 2001, doi: 10.1161/hh0202.103713
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© 2002 American Heart Association, Inc.
Clinical Research |
Effect of ATP-Sensitive Potassium Channel Inhibition on Resting Coronary Vascular Responses in Humans
From the Centre for Heart and Chest Research, Monash Medical Centre and Monash University, Melbourne, Australia.
Correspondence to Assoc Prof Ian T. Meredith, Cardiovascular Research Centre, Monash Medical Centre, 246 Clayton Rd, Clayton, Melbourne, Victoria, 3168, Australia. E-mail ian.meredith{at}med.monash.edu.au
Experimental data suggest that vascular ATP-sensitive potassium (KATP) channels regulate coronary blood flow (CBF), but their role in regulating human CBF is unclear. We sought to determine the contribution of KATP 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 KATP 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 (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 KATP channels are involved in the maintenance of basal coronary tone but may not be essential to adenosine-induced coronary hyperemia in humans.
Key Words: blood flow • potassium channels • sulfonylurea • vasoconstriction • coronary flow reserve
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