Location as a determinant of myocardial infarction in rabbits

Determinants of infarct size in the rabbit heart include risk zone size, regional myocardial blood flow (RMBF), temperature and duration of ischemia. However, other factors might contribute, such as the location of the risk zone (apex to base), independent of known factors. Occlusion of a large marginal branch of the circumflex artery in the rabbit produces a risk region that typically comprises the entire apex of the left ventricle with decreasing area involvement from apex to base. In a retrospective study of 65 rabbit hearts (subjected to 30 min of coronary artery occlusion) which had been sliced into six to eight cross-sectional slices, average area at risk (AR) comprised 86+/-3% of the apical level, 68+/-2% of the middle level and 39+/-2% near the site of occlusion at the base of the heart. If necrosis were dependent on AR alone, then infarct size (area of necrosis/area at risk, AN/AR) would not vary by site. However, AN/AR in the apex was 54+/-3% while AN/AR near the base was 27+/-2%, P<0.0001. To test if this salvage of tissue at risk near the base was due to differences in regional myocardial blood flow, we measured RMBF during occlusion in additional rabbits (n=4). Average RMBF in the risk zone was 0.025 ml/min/g in the apex and 0.010 in the base, P=N.S. Nor was the salvage due to differences in temperature. During occlusion, temperature in the risk zone (n=5) was 38.1 degrees C+/-0.3 in the apex and 38.4+/-0.2 in the base (P=N.S.). When we examined this phenomenon in hearts that received a non-pharmacological intervention that decreases overall infarct size (ischemic preconditioning) and in hearts that received a pharmacological intervention that decreases overall infarct size, a similar pattern of decreasing infarct size as a percentage of the area at risk from apex to base was observed. In conclusion, infarct size as a percentage of the AR depends on whether the AR is at the apex or base of the heart. A larger part of the AR undergoes necrosis toward the apex of the heart. This phenomenon is independent of collateral flow or temperature, and suggests that other as yet unknown factors contribute to infarct size.