Oral hypoglycemic sulfonylurea glimepiride preserves the myoprotective effects of ischemic preconditioning.
BACKGROUND
To investigate whether the sulfonylurea glimepiride affects the myoprotective effects of ischemic preconditioning (IPC), isolated rabbit hearts were perfused with Krebs-Henseleit solution.


METHODS
Eight hearts underwent IPC consisting of two cycles of 5 min global ischemia and reperfusion. Six hearts received a 5-min infusion of 10 microM glimepiride, six hearts received a 5-min infusion of 50 microM glimepiride, and seven hearts received a 5-min infusion of 10 microM glibenclamide before IPC. Seven hearts received a 5-min infusion of the selective mitochondrial K(ATP) channel opener diazoxide (50 microM). Other hearts received a 5-min infusion of 10 microM glimepiride (n = 6), 50 microM glimepiride (n = 6), or 10 microM glibenclamide (n = 7) before diazoxide. Seven hearts served as a control. All groups then were subjected to 1 h of regional ischemia, followed by 1 h of reperfusion. LV pressures, monophasic action potential duration (APD(50)), and infarct size were measured.


RESULTS
Both IPC and diazoxide significantly prolonged APD(50) and preserved diastolic function at 60 min of reperfusion compared to control. In addition, both groups reduced infarct size compared to control. Glibenclamide, but not glimepiride reversed these effects.


CONCLUSIONS
Glimepiride offers less cardiovascular effects than glibenclamide, possibly due to its lower affinity for the mitochondrial K(ATP) channels.
Horimoto
Hitoshi
H
Department of Thoracic and Cardiovascular Surgery, Osaka Medical College, Takatsuki, Osaka, Japan. tho043@poh.osaka-med.ac.jp
Nakai
Yasunari
Y
Mieno
Shigetoshi
S
Nomura
Yukiya
Y
Nakahara
Kenichi
K
Sasaki
Shinjiro
S
D000200:Action Potentials; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D011312:Pressure; D011817:Rabbits; D011930:Reaction Time; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D016277:Ventricular Function, Left
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; C057619:glimepiride