Metabolic Mechanism by Which Mild Regional Hypothermia Preserves Ischemic Tissue

Abstract

Background: 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 µmoles ATP/g wet tissue vs 0.84 ± 0.06 µmoles ATP/g wet tissue and 8.16 ± 0.95 µmoles of glucosyl unit/g wet tissue vs 4.43 ± 0.44 µmoles 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.