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 (<or= 2.5 degrees 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 degrees C) throughout the experiment (W-W-W group). All other animals were cooled to reduce left atrial temperature 2.0 degrees C to 2.5 degrees 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 < 1 x 10(-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.
Kanemoto
Shinya
S
Harrison Department of Surgical Research, Glenolden Research Laboratory, University of Pennsylvania, Glenolden, Pennsylvania 19036, USA.
Matsubara
Muneaki
M
Noma
Mio
M
Leshnower
Bradley G
BG
Parish
Landi M
LM
Jackson
Benjamin M
BM
Hinmon
Robin
R
Hamamoto
Hirotsugu
H
Gorman
Joseph H
JH
Gorman
Robert C
RC
D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D004195:Disease Models, Animal; D007036:Hypothermia, Induced / Q000379:methods*; D007150:Immunohistochemistry; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D017202:Myocardial Ischemia / Q000517:prevention & control / Q000628:therapy*; D015425:Myocardial Reperfusion / Q000379:methods; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D011336:Probability; D011817:Rabbits; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D013997:Time Factors