title: Myocardial protection with monophosphoryl lipid-A against aortic cross clamping-induced global stunning.
abstract: BACKGROUND
  Monophosphoryl lipid-A (MLA) has a late window (24 hours) of cardioprotection against acute myocardial infarction. It is not known whether MLA, administered, 24 hours before surgery, attenuates intraoperative ventricular dysfunction "stunning" associated with aortic cross-clamping and reperfusion during elective cardiac surgery. We determined the dose-response relationship between MLA and ventricular function in a canine model of global myocardial stunning in the absence of necrosis. The role of expression of inducible heat shock protein 70 (HSP 70i) was also investigated.
  
  
  METHODS
  Mongrel dogs (n = 32) were intravenously injected with either a vehicle solution or 3, 5, 10, 35 ug/kg MLA. Twenty four hours later, dogs were anesthetized and instrumented, in situ, to monitor the left ventricular performance (the slope of regression between stroke-work and end diastolic length). Tissue samples were obtained to determine HSP70i using immunoblot analysis. After a period of equilibration on cardiopulmonary bypass, the aortic cross-clamp was applied at normothermia for 30 minutes followed by 60 minutes of reperfusion. ATP and catabolites were determined in transmural myocardial biopsies. Triphenyl-tetrazolium chloride (TTC) staining was used to determine myocardial necrosis.
  
  
  RESULTS
  MLA treatment did not alter myocardial contractility or ATP metabolism. Global ischemia resulted in about 50% depletion of ATP and remained depressed during reperfusion in all groups. MLA-treated hearts had improved functional recovery in a dose dependent-manner. Significant recovery was observed at the highest dose (35 ug/kg) compared to the control group. Immunoblot analysis demonstrated significant increase in HSP 70i in the MLA-treated hearts.
  
  
  CONCLUSIONS
  MLA exhibits a delayed (24 hours) window of protection against myocardial stunning associated with aortic cross-clamping. HSP70i expression may play a role in MLA-mediated cardioprotection.
authors.affiliation: Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0532, USA. anwar@hsc.ucu.edu
authors.forename: A S
authors.initials: AS
authors.lastname: Abd-Elfattah
authors.forename: J H
authors.initials: JH
authors.lastname: Guo
authors.forename: S P
authors.initials: SP
authors.lastname: Goa
authors.forename: G A
authors.initials: GA
authors.lastname: Elliot
authors.forename: P
authors.initials: P
authors.lastname: Weber
authors.forename: M A
authors.initials: MA
authors.lastname: Mahgoub
authors.forename: R
authors.initials: R
authors.lastname: Marktanner
authors.forename: A
authors.initials: A
authors.lastname: Mohamed
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007275:Injections, Intravenous; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D017682:Myocardial Stunning / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis
chemical_list: D000276:Adjuvants, Immunologic; D018840:HSP70 Heat-Shock Proteins; D008050:Lipid A; C048436:monophosphoryl lipid A