THE EFFECT OF INTRACORONARY GLIBENCLAMIDE ON
CORONARY BLOOD FLOW AND CORONARY FLOW RESERVE IN PATIENTS WITH CORONARY ARTERY
DISEASE. H.M.O Farouque, R.A.P Skyrme-Jones, M.J Zhang & I.T Meredith Centre for Heart & Chest Research, Monash University, Monash
Medical Centre, Melbourne. Glibenclamide (glib) is widely used in the
treatment of type 2 diabetes (DM). The insulin releasing effect of this agent
is based on blockade of ATP-sensitive potassium (KATP) channels in
pancreatic beta cells. Recent evidence suggests KATP channels are
also present on vascular smooth muscle cells and may contribute to blood flow
regulation. We therefore assessed the
effect of acute KATP channel inhibition following the infusion of
intracoronary (IC) glib in patients with known coronary artery disease. Eight male patients (53±14 years, mean±SD), 5 of
whom had DM who were scheduled for elective coronary angioplasty were recruited
for this study. Resting coronary blood flow (CBF) and coronary flow reserve
(CFR) were assessed in an angiographically smooth or mildly irregular
non-angioplastied coronary artery using a 0.014" coronary Doppler flow
wire. IC glib was subselectively
infused at 4mg/minute, 16mg/minute and 40mg/minute
each for 5 minutes via a 2.8F infusion catheter. The doses were calculated to
attain an estimated final IC concentration of 5ng/ml, 200ng/ml and 500ng/ml
respectively. CBF was calculated from the product of basal average peak
velocity (APV) determined from coronary Doppler flow velocimetry and coronary cross-sectional
area obtained by quantitative coronary angiography. CFR was measured following
IC boluses of 24mg of adenosine at the end of each glib
infusion. Compared to vehicle infusion (0.9% saline), IC glib at the 3 doses
assessed did not alter conduit vessel diameter (2.7±0.2 vs 2.6±0.2 vs
2.6±0.2 vs 2.5±0.2 mm), APV (21.8±2.2
vs 22.6±1.7 vs 23.9±2.5 vs
23.8±2.1 cm/sec), CBF (61.5±9.6 vs 62.5±9.5 vs
63.3±12.1 vs 59.8±9.5 mL/min) or CVR (1.7±0.3 vs 1.7±0.3 vs
1.8±0.3 vs 1.9±0.3 mmHg·mL-1·min-1). CFR was similarly unchanged (2.7±0.3 vs 2.6±0.3 vs
2.4±0.2 vs 2.5±0.2). There were no effects on heart rate or blood pressure.
Similarly glucose, insulin and C-peptide levels were also unchanged. In
patients with coronary artery disease, IC glib (4mg/minute to 40ug/minute) has no demonstrable effect on CBF or CFR
acutely. This may be because redundant
vasodilator mechanisms such as NO-mediated or prostacylin-mediated vasodilation
may offset the effect of KATP channel inhibition.
