title: Regional heterogeneity of myocardial reperfusion injury: effect of mild hypothermia.
abstract: BACKGROUND
  Mild hypothermia confers a myocardial protective effect that may make it a useful adjunct to reperfusion therapy for myocardial infarction (MI). The effect of temperature on the extent and distribution of myocardial reperfusion injury in a collateral deficient ovine model was studied.
  
  
  METHODS
  Topical cooling maintained left atrial temperature at 39.5 degrees C (n = 8), 38.5 degrees C (n = 5), 37.5 degrees C (n = 6), 36.5 degrees C (n = 6), or 35.5 degrees C (n = 5) in sheep prior to 1 hour of coronary occlusion to produce an anteroapical myocardial risk area (AR) followed by 3 hours of reperfusion. A dual staining and planimetry technique was used to assess infarct size as a percentage of the AR in 3 myocardial short axis slices that included the entire AR (slice 1= most apical; slice 3= most basal). The subendocardial, midmyocardial, and subepicardial extent in short axis of the infarct was also assessed in each slice. Microspheres assessed transmural blood flow.
  
  
  RESULTS
  At 39.5 degrees C there was a long-axis gradient in myocardial injury that was most severe at the apex and lessened toward the base. The midmyocardial region was most susceptible to injury at all long axis levels. Temperature reduction (as little as 1 degrees C) was associated with improved salvage that was most pronounced in the apical subendocardium and least in the basilar midmyocardium. Reperfusion at 39.5 degrees C resulted in severe transmural microvascular injury (no-reflow) that was completely obviated at temperatures below 38.5 degrees C.
  
  
  CONCLUSIONS
  Myocardial reperfusion injury varies over the long and short LV axes. Mild hypothermia preferentially improves myocardial salvage at the LV apex. Small temperature changes can dramatically affect microvascular integrity.
authors.affiliation: Harrison Department of Surgical Research, Glenolden Research Laboratory, University of Pennsylvania, Glenolden, Pennsylvania 19036, USA.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Hamamoto
authors.forename: Bradley G
authors.initials: BG
authors.lastname: Leshnower
authors.forename: Landi M
authors.initials: LM
authors.lastname: Parish
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Shinya
authors.initials: S
authors.lastname: Kanemoto
authors.forename: Robin
authors.initials: R
authors.lastname: Hinmon
authors.forename: Shinji
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Gorman
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gorman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D004195:Disease Models, Animal; D007036:Hypothermia, Induced / Q000379:methods*; D007150:Immunohistochemistry; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D009203:Myocardial Infarction / Q000473:pathology* / Q000628:therapy*; D015425:Myocardial Reperfusion / Q000379:methods; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D012756:Sheep; D013696:Temperature; D020257:Ventricular Remodeling / Q000502:physiology