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.

Fig 1

Sheep left ventricular (LV) sections sliced perpendicular to its long axis after staining with Evans blue dye to delineate the risk area. Slice 1 is the most apical region. Slice 3 is most basilar, located approximately halfway between the apex and base of the LV.

Fig 2

Photographs with planimetry tracings of the ovine left ventricle sliced perpendicular to its long axis. (A) Evans blue dye staining to delineate the ischemic area at risk (AR). The AR is the unstained myocardium. (B) triphenyltetrazolium chloride (TTC) staining to delineate viable (brick red) from nonviable (pale) myocardium in the AR. (C) technique for transmural analysis. The AR is divided into equally sized subendocardium, midmyocardium, and subepicardium regions.

Fig 3

Left atrial temperature for each group of animals over time for the entire duration of the experiment. Temperature was maintained very close to goal values for all animals in all groups.

Fig 4

Infarct size as a percentage of the myocardial area at risk (I/AR) for each left ventricular slice at varying levels of hypothermia. (^ap < 0.05 vs 39.5°C; ^bp < 0.05 vs 38.5°C; ^cp < 0.05 vs 37.5°C; ^dp < 0.05 vs 36.5°C; ^ep < 0.05 vs slice 1; ^fp < 0.05 vs Slice 2.

Fig 5

Normalized blood flow in a transmural region of myocardium within the area at risk of slice 2 at varying levels of hypothermia. Data are presented as a percentage of baseline pre-ischemic blood flow. (^ap < 0.05 vs 39.5°C; ^bp < 0.05 vs ischemia; ^cp < 0.05 vs reperfusion (10 minutes).