title: Effects of sulfonylurea derivatives on ischemia-induced loss of function in the isolated rat heart.
abstract: This study determined whether sulfonylurea derivatives affect cardiac function prior to and after a mild ischemic incident (stunning). This was investigated using an isolated, erythrocyte-perfused, working rat heart model. In total, 11 groups were studied: five increasing (clinically relevant) concentrations of the classical glibenclamide (range 0.005-4 micromol l(-1)), five increasing concentrations of the newly developed glimepiride (range 0.005-0.8 micromol l(-1)), and one control group. Pre-ischemically, glibenclamide and glimepiride reduced coronary blood flow concentration dependently to 55.2+/-4.5% and 58.5+/-5.5%, respectively (P<0.001). Twenty minutes after a 12-min ischemic incident, these reductions of flow were even more pronounced (to 38.3+/-6.7% and 45.8+/-5.8%, P<0.001). This shows that both sulfonylureas reduce coronary blood flow at concentrations slightly higher than therapeutic ones. In the control group, the ischemic incident significantly lowered cardiac function by 22.2+/-2.9%. In the therapeutic range, glimepiride, but not glibenclamide, significantly reduced this ischemia-induced cardiac functional loss to 4.9+/-1.2% (P<0.01). Therefore, we suggest that both sulfonylureas and in particular glimepiride can be used safely in patients with type 2 diabetes mellitus, as long as the coronary vascular system is not compromised. Because of the obvious vasocontrictor response to sulfonylurea derivatives, these drugs must be used with caution in patients with a reduced coronary reserve.
authors.affiliation: Department of Physiology 237, University Medical Center Nijmegen, P.O. Box 9101, NL-6500 HB, Nijmegen, Netherlands. r.legtenberg@fysio.kun.nl
authors.forename: R J
authors.initials: RJ
authors.lastname: Legtenberg
authors.forename: R J
authors.initials: RJ
authors.lastname: Houston
authors.forename: B
authors.initials: B
authors.lastname: Oeseburg
authors.forename: P
authors.initials: P
authors.lastname: Smits
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D017682:Myocardial Stunning / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D013453:Sulfonylurea Compounds; C057619:glimepiride; D005905:Glyburide