title: 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.
abstract: OBJECTIVE
  To investigate whether blood flow in normal and post-stenotic coronary arteries is altered by therapeutic doses of the sulfonylurea agent glibenclamide.
  
  
  METHODS
  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.
  
  
  METHODS
  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 microg 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 beta 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.
authors.affiliation: Medizinische Klinik I, University Hospital, Rheinisch-Westfälische Technische Hochschule (RWTH), Pauwelsstrasse 30, D-52057 Aachen, Germany. thorstenreffelmann@web.de
authors.forename: T
authors.initials: T
authors.lastname: Reffelmann
authors.forename: H G
authors.initials: HG
authors.lastname: Klues
authors.forename: P
authors.initials: P
authors.lastname: Hanrath
authors.forename: E R
authors.initials: ER
authors.lastname: Schwarz
mesh_terms: D000284:Administration, Oral; D001786:Blood Glucose / Q000032:analysis; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects; D023921:Coronary Stenosis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005905:Glyburide / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000097:blood
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; C050632:polypeptide C; D005905:Glyburide