Preconditioning of swine heart with monophosphoryl lipid A improves myocardial preservation

Background. Ischemic preconditioning has been proven to be a powerful tool for myocardial protection in the setting of ischemia and reperfusion. A new drug to provide pharmacologic preconditioning, monophosphoryl lipid A (MLA ), was administered 24 hours before an acute coronary occlusion in pigs to determine the effect on pharmacologic preconditioning. Methods. Two studies were completed. In the first, swine were distributed i nto five groups: group I, control; group II,. aminoguanidine (AMG) (30 mg/k g), a selective inducible nitric oxide synthase (iNOS) blocker; group III, MLA (10 mu g/kg); group IV, MLA (35 mu g/kg); and group V, MLA and AMG (35 mu g/kg and 30 mg/kg, respectively). Twenty-four hours after administration of the MLA, AMG, or both, regional left anterior descending coronary arter y ischemia was induced for 15 minutes followed by one hour of global normot hermic cardioplegic arrest and three hour reperfusion. Left ventricular fun ction, tissue injury, and percentage of myocardial infarction were measured . Left ventricular myocardium in the left anterior descending coronary arte ry region was sampled for iNOS messenger RNA (mRNA) during ischemia and rep erfusion. In the second study, pigs were sacrificed 0, 4, 6, 8, and 24 hrs after MLA/AMG administration for iNOS mRNA determination in nonischemic myo cardium. Results. Use of MLA significantly improved postischemic ventricular functio n, and reduced creatinine kinase release and percentage of infarction. Mono phosphoryl lipid A induced expression of iNOS mRNA in nonischemic myocardiu m within four hours of administration which returned to base line by 24 hou rs. Normothermic regional ischemia then induced expression of iNOS mRNA, wh ich returned to base line during reperfusion. Aminoguanidine completely abo lished both MLA-induced and ischemia-induced iNOS mRNA and blocked the bene ficial effects of MLA. Conclusions. Use of MLA can provide myocardial preservation through enhance d expression of iNOS mRNA. (Ann Thorac Surg 2000;70:895-900) (C) 2000 by Th e Society of Thoracic Surgeons.