Dose-Dependent Cardioprotection of Moderate 32 degrees C) Versus Mild (35 degrees C) Therapeutic Hypothermia in Porcine Acute Myocardial Infarction

Abstract

OBJECTIVES The study investigated whether a dose response exists between myocardial salvage and the depth of therapeutic hypothermia. BACKGROUND Cardiac protection from mild hypothermia during acute myocardial infarction (AMI) has yielded equivocal clinical trial results. Rapid, deeper hypothermia may improve myocardial salvage. METHODS Swine (n = 24) undergoing AMI were assigned to 3 reperfusion groups: normothermia (38 degrees C) and mild (35 degrees C) and moderate (32 degrees C) hypothermia. One-hour anterior myocardial ischemia was followed by rapid endovascular cooling to target reperfusion temperature. Cooling began 30 min before reperfusion. Target temperature was reached before reperfusion and was maintained for 60 min. Infarct size (IS) was assessed on day 6 using cardiac magnetic resonance, triphenyl tetrazolium chloride, and histopathology. RESULTS Triphenyl tetrazolium chloride area at risk (AAR) was equivalent in all groups (p = 0.2), but 32 degrees C exhibited 77% and 91% reductions in IS size per AAR compared with 35 degrees C and 38 degrees C, respectively (AAR: 38 degrees C, 45 +/- 12%; 35 degrees C, 17 perpendicular to 10%; 32 degrees C, 4 perpendicular to 4%; p < 0.001) and comparable reductions per LV mass (LV mass: 38 degrees C, 14 +/- 5%; 35 degrees C, 5 perpendicular to 3%; 32 degrees C 1 +/- 1%; p < 0.001). Importantly, 32 degrees C showed a lower IS AAR (p = 0.013) and increased immunohistochemical granulation tissue versus 35 degrees C, indicating higher tissue salvage. Delayed-enhancement cardiac magnetic resonance IS LV also showed marked reduction at 32 degrees C (38 degrees C: 10 +/- 4%, p < 0.001; 35 degrees C: 8 +/- 3%; 32 degrees C: 3 +/- 2%, p < 0.001). Cardiac output on day 6 was only preserved at 32 degrees C (reduction in cardiac output: 38 degrees C, -29 +/- 19%, p = 0.041; 35 degrees C: -17 +/- 33%; 32 degrees C: -1 +/- 28%, p = 0.041). Using linear regression, the predicted IS reduction was 6.7% (AAR) and 2.1% (LV) per every 1 degrees C reperfusion temperature decrease. CONCLUSIONS Moderate (32 degrees C) therapeutic hypothermia demonstrated superior and near-complete cardioprotection compared with 35 degrees C and control, warranting further investigation into clinical applications. (J Am Coll Cardiol Intv 2018; 11: 195-205) (C) 2018 by the American College of Cardiology Foundation.