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Delta opioid agonists and volatile anesthetics facilitate cardioprotection via potentiation of K ATP channel opening
Author(s) -
Patel Hemal H.,
Ludwig Lynda M.,
Fryer Ryan M.,
Hsu Anna K.,
Warltier David C.,
Gross Garrett J.
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0170fje
Subject(s) - isoflurane , diazoxide , cardioprotection , glibenclamide , naltrindole , potassium channel , pharmacology , potassium channel blocker , chemistry , cromakalim , channel blocker , atp sensitive potassium channel , anesthetic , potassium channel opener , opioid , anesthesia , medicine , (+) naloxone , myocardial infarction , endocrinology , receptor , insulin , calcium , diabetes mellitus
Opioids and volatile anesthetics produce marked cardioprotective effects against myocardial infarction via the activation of ATP‐sensitive potassium (K ATP ) channels, however, the effect of combined treatment with both drugs is unknown. We examined the hypothesis that opioids and volatile anesthetics potentiate cardiac K ATP channel opening, thereby enhancing cardioprotection. Rats were treated with the delta opioid agonists, TAN‐67 or BW373U86, or isoflurane, together or alone with and without diazoxide, a mitochondrial K ATP channel opener. Glibenclamide, a non‐selective K ATP channel blocker, was used to further characterize the signaling mechanism involved. Myocardial infarct size (IS) was determined by tetrazolium staining and was expressed as a percent of the area at risk (AAR). High doses of TAN‐67 (10 mg/kg), diazoxide (10 mg/kg), and isoflurane (1 MAC) produced a significant reduction in IS compared with the control group (30±3%, 36±5%, and 42±2 vs. 58±2%, respectively), whereas lower doses of the drugs had no effect except for the low dose of isoflurane (0.5 MAC). The combination of TAN‐67 and diazoxide or isoflurane and diazoxide resulted in a marked reduction in IS compared with controls in the presence of high (9±3% and 14±3%) and low (17±7% and 31±7%) dose combinations, respectively. The combination of TAN‐67 or BW373U86 and isoflurane also caused a striking reduction in IS/AAR (16±7% and 7±2%, respectively). To date, this is the first demonstration that opioids and volatile anesthetics work in conjunction to confer protection against myocardial infarction through potentiation of cardiac K ATP channel opening.