Faculty Collaboration Database

Delta opioid agonists and volatile anesthetics facilitate cardioprotection via potentiation of K(ATP) channel opening. FASEB J 2002 Sep;16(11):1468-70

Date

09/03/2002

Pubmed ID

12205051

DOI

10.1096/fj.02-0170fje

Scopus ID

2-s2.0-0036717152 (requires institutional sign-in at Scopus site)   55 Citations

Abstract

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.

Author List

Patel HH, Ludwig LM, Fryer RM, Hsu AK, Warltier DC, Gross GJ

Author

David C. Warltier PhD Emeritus Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Anesthetics, Inhalation
Animals
Benzamides
Cardiotonic Agents
Diazoxide
Drug Synergism
Isoflurane
Models, Cardiovascular
Myocardial Infarction
Myocardium
Narcotics
Piperazines
Potassium Channels
Quinolines
Rats
Receptors, Opioid, delta