Pharmacologic preconditioning with monophosphoryl lipid A is abolished by 5-hydroxydecanoate, a specific inhibitor of the K(ATP) channel.
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.
Janin
Y
Y
Division of Cardiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
Qian
Y Z
YZ
Hoag
J B
JB
Elliott
G T
GT
Kukreja
R C
RC
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006880:Hydroxy Acids / Q000494:pharmacology*; D019194:Ischemic Preconditioning; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D009203:Myocardial Infarction / Q000188:drug therapy*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D026902:Potassium Channel Blockers; D011817:Rabbits
D003652:Decanoic Acids; D006880:Hydroxy Acids; D008050:Lipid A; D026902:Potassium Channel Blockers; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C048436:monophosphoryl lipid A