Myocardial temperature reduction attenuates necrosis after prolonged ischemia in rabbits.

Abstract

Previously we observed that a large reduction in infarct size was attained by cooling the risk region of the heart, either before or early after the onset of a 30-min coronary artery occlusion. While this is a standard duration of ischemia used in the rabbit model of infarction, it may not reflect the situation of patients who are reperfused late. The effects of regional hypothermia with a longer duration of ischemia, and when the intervention is applied later, are unknown. This study tests the hypothesis that a local reduction in cardiac temperature protects myocardium during prolonged ischemia (2 h) even if begun well after coronary artery occlusion. Anesthetized rabbits received 2 h of coronary artery occlusion and 3 h of reperfusion. Rabbits were randomly assigned to a treated group: topical myocardial cooling starting 30 min after coronary occlusion (n = 14), or control group, no intervention (n = 12). Myocardial temperature in the risk zone, hemodynamics and regional myocardial blood flow were measured. Ischemic zone temperature was similar in both groups at 30 min post occlusion, but the cooling maneuver produced a reduction in temperature in the risk region of the treated group such that myocardial temperature was reduced an average of 10 degrees C between 30 and 60 min of coronary artery occlusion. Myocardial temperature in the control group remained within 0.3 degree C of baseline during coronary artery occlusion and into reperfusion. Core temperatures were similar in both groups. Hemodynamic parameters and collateral blood flow during occlusion were also equivalent in both groups. After 120 min of coronary occlusion, necrosis in the control group comprised 72 +/- 3% of the ischemic risk region. However, in cooled hearts, infarct size, expressed as a fraction of the risk region was significantly lower. Infarct size in this group averaged 59 +/- 3% of the risk region (p < 0.004 vs. controls), and thus cooling resulted in a salvage of approximately 18% of the risk region. These results show that reducing myocardial temperature protects ischemic myocardium during a long duration of ischemia even if initiated after coronary artery occlusion.