Linked Life Data

16382296

Source:http://linkedlifedata.com/resource/pubmed/id/16382296

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-12-29
pubmed:abstractText
The K(ATP) channel blocker glibenclamide inhibits cardioprotection afforded by ischemic preconditioning (IPC), raising concern about sulfonylurea use by patients with cardiovascular disease. We examined the effects of the widely prescribed sulfonylurea glipizide (Glucotrol XL(R) ) on IPC in anesthetized rabbits. Initially, in parallel studies in pentobarbital-anesthetized rabbits, we identified doses of glipizide (GLIP, 0.17 mg/kg + 0.12 mg/kg/h, IV) and glibenclamide (GLIB, 0.05 mg/kg + 0.03 mg/kg/h, IV) that produced steady-state, clinically relevant plasma levels of both drugs; these doses also significantly increased plasma insulin by 51 +/- 17% (GLIP) and by 57 +/- 17% (GLIB, both p < 0.05 vs. their respective baseline levels). Subsequent parallel studies in ketamine-xylazine-anesthetized rabbits examined the effects of these doses of GLIP and GLIB on IPC. Myocardial injury (30 min coronary occlusion/120 min reperfusion), either with or without IPC (5 min occlusion/10 min reperfusion) was induced midway during a 2 h infusion of vehicle (VEH), GLIP or GLIB (n = 10-11 each). Infarct area (IA) normalized to area-at-risk (%IA/AAR) was 62 +/- 3% in the VEH group, and was significantly reduced to 39 +/- 5% by IPC (p < 0.05 vs. VEH). Neither GLIP nor GLIB treatment had any effect on %IA/AAR in the absence of IPC (p > 0.05). IPC-induced cardioprotection was preserved in the GLIP + IPC treatment group (45 +/- 4%) when compared to VEH alone (p < 0.05), but was attenuated in the presence of GLIB (GLIB+IPC: 53 +/- 4% IA/AAR, p > 0.05 vs. VEH). Thus, at a clinically relevant plasma concentration, glipizide did not limit the cardioprotective effects of IPC, and is unlikely to increase the severity of cardiac ischemic injury.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0920-3206
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
337-46
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
The sulfonylurea glipizide does not inhibit ischemic preconditioning in anesthetized rabbits.
pubmed:affiliation
Department of Cardiovascular, Metabolic and Endocrine Diseases, Pfizer Global Research and Development, Pfizer Inc., Groton, CT 06340, USA.
pubmed:publicationType
Journal Article, Comparative Study