Glimepiride, a Novel Sulfonylurea, Does Not Abolish Myocardial Protection Afforded by Either Ischemic Preconditioning or Diazoxide

Abstract

Background-The sulfonylurea glibenclamide (Glib) abolishes the cardioprotective effect of ischemic preconditioning (IP), presumably by inhibiting mitochondrial K ATP channel opening in myocytes. Glimepiride (Glim) is a new sulfonylurea reported to affect nonpancreatic K ATP channels less than does Glib. We examined the effects of Glim on IP and on the protection afforded by diazoxide (Diaz), an opener of mitochondrial K ATP channels. Methods and Results-Rat hearts were Langendorff-perfused, subjected to 35 minutes of regional ischemia and 120 minutes of reperfusion, and assigned to 1 of the following treatment groups: (1) control; (2) IP of 2ϫ 5 minutes each of global ischemia before lethal ischemia; or pretreatment with (3) 30 mol/L Diaz, (4) 10 mol/L Glim, (5) 10 mol/L Glib, (6) IPϩGlim, (7)

Effect of metabolic inhibition on glimepiride block of native and cloned cardiac sarcolemmal KATP channels

“…It has also been shown recently that glimepiride, unlike glibenclamide, does not abolish the cardioprotective e ects of IPC (Klepzig et al, 1999;Mocanu et al, 2001). A possible explanation for these ®ndings is that the observed protection is conferred by mitochondrial, rather than sarcolemmal, K ATP channels (Grover & Garlid, 2000) and that these channels are una ected by glimepiride.…”

“…In contrast to glibenclamide, however, glimepiride does not appear to abolish IPC (Klepzig et al, 1999;Mocanu et al, 2001). It has been postulated therefore, that glimepiride has selective e ects between di erent K ATP channels (Ladriene et al, 1997;Olbrich et al, 1999).…”

Is Metformin Cardioprotective?

“…However, it is now generally accepted that the UKPDS put that issue to rest by finding no increased rate of myocardial infarction or mortality with sulfonylurea usage (3,6). Moreover, a potential causative mechanism of CV jeopardy with sulfonylureas, impaired ischemic preconditioning, is seemingly not evident with newer sulfonylureas, such as glimepiride compared with glyburide (15,16). Perhaps of most interest in terms of CV protection is the thiazolidinedione ("glitazone") class of drugs.…”

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