Pharmacologic preconditioning with monophosphoryl lipid A is abolished by 5-hydroxydecanoate, a specific inhibitor of the K(ATP) channel.
Publication/Presentation Date
9-1-1998
Abstract
We sought to determine the role of opening of adenosine triphosphate (ATP)-sensitive potassium channel (K(ATP) channel) in monophosphoryl lipid A (MLA)-induced myocardial protection after ischemia/reperfusion (I/R) in rabbit. We used 5-hydroxydecanoate (5-HD), an ischemia-selective inhibitor of K(ATP) channel, to block MLA-stimulated cardiac protection. Four groups of rabbits were studied: group I, MLA-vehicle; group II, MLA; group III, MLA + 5-HD; and group IV, 5-HD only. MLA (35 microg/kg, i.v.) or vehicle were given 24 h before I/R. 5-HD (5 mg/kg) was given 15 min before ischemia. All rabbits underwent 30-min coronary occlusion, followed by 3-h reperfusion. Area at risk was delineated by injection of Evan's blue, and infarct size was determined by tetrazolium staining. Pretreatment with MLA reduced infarct size (percentage of area at risk) from 40+/-8.6% to 15.1+/-1.5%. The infarct size increased to 51.9+/-5.8% with 5-HD in MLA-treated rabbits. 5-HD did not alter infarct size significantly when given in vehicle-treated control rabbits. These data suggest that MLA exerts its protective effect through activation of K(ATP) channel.
Volume
32
Issue
3
First Page
337
Last Page
342
ISSN
0160-2446
Published In/Presented At
Janin, Y., Qian, Y. Z., Hoag, J. B., Elliott, G. T., & Kukreja, R. C. (1998). Pharmacologic preconditioning with monophosphoryl lipid A is abolished by 5-hydroxydecanoate, a specific inhibitor of the K(ATP) channel. Journal of cardiovascular pharmacology, 32(3), 337–342. https://doi.org/10.1097/00005344-199809000-00001
Disciplines
Medicine and Health Sciences
PubMedID
9733344
Department(s)
Department of Medicine
Document Type
Article