PHARMACOLOGICAL 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 lip id A (MLA)-induced myocardial protection after ischemia/reperfusion (I /R) in rabbit. We used 5-hydroxydecanoate (5-HD), an ischemia-selectiv e inhibitor of K-ATP channel, to block MLA-stimulated cardiac protecti on. Four groups of rabbits were studied: group I, MLA-vehicle; group I I, MLA; group III, MLA + 5-HD; and group IV, 5-HD only. MLA (35 mu g/k g, i.v.) or vehicle were given 24 h before I/R. 5-HD (5 mg/kg) was giv en 15 min before ischemia. All rabbits underwent 30-min coronary occlu sion, followed by 3-h reperfusion. Area at risk was delineated by inje ction of Evan's blue, and infarct size was determined by tetrazolium s taining. Pretreatment with MLA reduced infarct size (percentage of are a at risk) from 40 +/- 8.6% to 15.1 +/- 1.5%. The infarct size increas ed to 51.9 +/- 5.8% with 5-HD in MLA-treated rabbits. 5-HD did not alt er infarct size significantly when given in vehicle-treated control ra bbits. These data suggest that MLA exerts its protective effect throug h activation of K-ATP channel.