Mild Hypothermia to Limit Myocardial Ischemia-Reperfusion Injury: Importance of Timing

Background Hypothermia during ischemia has been shown to reduce myocardial reperfusion injury. We sought to establish the cardioprotective effect of very mild total-body hypothermia (≤ 2.5°C) and to determine whether the application of hypothermia at different points during the ischemia-reperfusion period influenced the degree of myocardial salvage. Methods Rabbits were subjected to 30 minutes of myocardial ischemia followed by 3 hours of reperfusion. Twenty-five animals were maintained at normal temperature (39.5°C) throughout the experiment (W-W-W group). All other animals were cooled to reduce left atrial temperature 2.0°C to 2.5°C. Eleven animals reached goal temperature before coronary occlusion (C-C-C group), in 14 animals cooling was initiated at coronary occlusion (W-C0-C group), in 8 animals cooling was initiated 15 minutes after coronary occlusion (W-C15-C group), in 5 animals cooling was initiated 25 minutes after coronary occlusion (W-C25-C group), and in 13 animals cooling was started concurrently with reperfusion (W-W-C group). Infarct size as a percentage of the risk area (I/AR) was determined by a double staining-planimetry technique. Results Goal temperature was achieved before reperfusion in the C-C-C and W-C0-C groups but was not achieved until the reperfusion period in the other treatment groups. Infarct size was 59.0 ± 1.2% in the W-W-W group and was reduced in all cooling groups (C-C-C = 30.4 ± 4.9%; W-C0-C = 33.4 ± 5.0%; W-C15-C = 42.4 ± 1.4%; W-C25-C = 44.1 ± 2.3%; W-W-C = 50.5 ± 4.1%). The temperature at reperfusion correlated most strongly with infarct size (r = 0.72, p −12 ). Conclusions Very mild hypothermia affords a significant cardioprotective effect. Temperature at the time of reperfusion most strongly correlates with the degree of myocardial salvage.