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Post-stenotic coronary blood flow at rest is not altered by therapeutic doses of the oral antidiabetic drug glibenclamide in patients with coronary artery disease

Medizinische Klinik I, University Hospital, Rheinisch-Westfälische Technische Hochschule (RWTH), Pauwelsstrasse 30, D-52057 Aachen, Germany

Correspondence to:
Correspondence to:
Dr T Reffelmann, Medizinische Klinik I, University Hospital, Rheinisch-Westfälische Technische Hochschule (RWTH), Pauwelsstrasse 30, D-52057 Aachen, Germany;
thorstenreffelmann{at}web.de

Objective: To investigate whether blood flow in normal and post-stenotic coronary arteries is altered by therapeutic doses of the sulfonylurea agent glibenclamide.

Patients: 12 patients with a high grade stenosis of the left anterior descending coronary artery (n = 10) or left circumflex coronary artery (n = 2), and an angiographically normal corresponding left circumflex artery or left anterior descending artery, respectively.

Design: Two Doppler ultrasound wires were positioned in the "normal" and post-stenotic artery for simultaneous measurements of coronary blood flow velocity under baseline conditions and after intravenous glibenclamide, 0.05 mg/kg body weight. Local coronary blood flow was calculated from the average peak velocity and the cross sectional area derived from quantitative coronary angiographic analysis. Coronary flow reserve was determined after intracoronary injection of 30 µg adenosine and 12 mg papaverine.

Results: One hour after glibenclamide, serum insulin increased from (mean (SD)) 7.4 (2.0) to 44.8 (25.5) mU/l (p < 0.005), and C peptide from 1.4 (0.4) to 3.4 (1.2) ng/l (p = 0.005). In normal coronary arteries coronary flow reserve was 2.6 (0.4) after adenosine and 3.0 (0.4) after papaverine, while in post-stenotic arterial segments it was 1.2 (0.3) after adenosine (p = 0.005) and 1.3 (0.3) after papaverine (p = 0.005). There was no significant difference after glibenclamide. In non-stenotic arteries, average peak velocity (18.8 (5.2) cm/s) and calculated coronary blood flow (23.8 (10.7) ml/min) were not altered by glibenclamide (18.3 (5.2) cm/s and 22.8 (10.4) ml/min, respectively). In post-stenotic arteries, baseline average peak velocity was 13.3 (4.9) ml/min and coronary blood flow was 9.1 (3.0) ml/min, without significant change after glibenclamide (13.3 (5.2) cm/s, 9.0 (3.2) ml/min).

Conclusions: Glibenclamide, 0.05 mg/kg intravenously, is effective in increasing serum insulin, suggesting a K_ATP channel blocking effect in pancreatic ß cells. It does not compromise coronary blood flow and vasodilatation in response to adenosine and papaverine in post-stenotic and angiographically normal coronary arteries at rest.

Keywords: coronary circulation; K_ATP channels; coronary artery disease; Doppler flow measurements

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