Our laboratory demonstrated that mild regional
hypothermia reduced
myocardial infarct size by an average of 65% in the rabbit model of regional
ischemia. The exact mechanism for this benefit has not been explored. We hypothesized that a moderate reduction in regional myocardial temperature could preserve cardiac energy metabolism and thus protect the myocardium from sustained ischemic insult.
METHODS AND RESULTS: Anesthetized open-chest rabbits were randomized to normothermic
sham-operated (NS, n = 6), hypothermic
sham-operated (HS, n = 6), normothermic ischemic (NI, n = 10), and hypothermic ischemic (HI, n = 10) groups. Both
sham-operated groups received no occlusions, and both ischemic groups were subjected to 20 minutes of
coronary occlusion. To achieve regional cooling of the hearts in the hypothermic groups, a bag of
ice water was placed directly on the risk area 15 minutes prior to coronary artery occlusion/no intervention and maintained for the duration of the subsequent 20 minutes of
ischemia/no intervention (in the HI and HS groups respectively).
Hypothermia preserved
adenosine triphosphate (
ATP) and
glycogen stores in the ischemic area by 42.9% and 84.2%, respectively (1.20 +/- 0.11 micromoles
ATP/g wet tissue vs 0.84 +/- 0.06 micromoles
ATP/g wet tissue and 8.16 +/- 0.95 micromoles of glucosyl unit/g wet tissue vs 4.43 +/- 0.44 micromoles of glucosyl unit/g wet tissue in the HI and the NI groups, respectively). In addition,
hypothermia resulted in a trend toward
creatine phosphate preservation in the nonischemic area.
CONCLUSIONS: This is the first demonstration that local
therapy with mild reductions in myocardial temperature preserves energy metabolism both in the ischemic and the nonischemic areas as well. The preservation in
ATP is the likely mechanism by which regional
hypothermia is preserving ischemic myocardium.