Regional hypothermia reduces myocardial necrosis even when instituted after the onset of ischemia

Abstract

Previously, we observed that reducing myocardial temperature in the risk region before coronary artery occlusion caused a profound reduction in infarct size. It is unknown whether lowering myocardial temperature after ischemia has already begun, or just before reperfusion, is also effective in reducing infarct size. This study tests the hypothesis that reducing myocardial temperature locally, after coronary occlusion, reduces infarct size.Methods: Anesthetized rabbits received 30 min of coronary artery occlusion and three hours of reperfusion. Myocardial temperature in the risk zone was monitored. Rabbits were randomly assigned to one of three groups: group 1, topical myocardial cooling starting 10 min after coronary occlusion (n=11); group 2, cooling starting 25 min after coronary occlusion (n=11); or group 3, control, no intervention (n=10).Results: Hemodynamic parameters and regional myocardial blood flow were equivalent in all groups. Risk zone temperature was similar in all groups at occlusion. The cooling maneuver produced a rapid reduction in temperature in the risk region. In group 1, myocardial temperature was reduced an average of 6.3°C between 10 and 15 min of coronary artery occlusion; myocardial temperature in group 2 was reduced an average of 5.9°C between 25 and 30 min of coronary artery occlusion. Cooling was maintained until 15 min of reperfusion. Myocardial temperature in group 3 remained within 0.3°C of baseline during coronary artery occlusion and into reperfusion. Core temperature was similar in all groups. Although the ischemic risk region was comparable in all groups, early cooling (group 1) resulted in a significant reduction in infarct size, expressed as a fraction of the risk region, compared with the control group (0.23±0.04 vs. 0.44±0.04 of the risk region); however, cooling just before reperfusion (group 2) failed to modify infarct size compared with the controls (0.43±0.04 and 0.44±0.04 of the risk region, respectively).Conclusion: These results support our hypothesis that reducing myocardial temperature reduces infarct size. However, it is important the reduction in temperature be produced as early as possible following coronary artery occlusion.