Extending Time to Reperfusion with Mild Therapeutic Hypothermia: A New Paradigm for Providing Primary Percutaneous Coronary Intervention to Remote ST Segment Elevation Myocardial Infarction Patients

Abstract

Primary percutaneous coronary intervention (PPCI) is the preferred treatment for acute ST segment elevation myocardial infarction (STEMI). The goal is reperfusion within 90 minutes of first medical contact (FMC) or 120 minutes if transfer is needed. Otherwise, fibrinolytic therapy is recommended. Mild therapeutic hypothermia (MTH) (≤35°C) before coronary reperfusion decreases myocardial infarct size. If applied before reperfusion, hypothermia could potentially lengthen the FMC-reperfusion time without increasing infarct size. Thirty-six swine had their mid left anterior descending coronary artery acutely occluded. All animals had an initial 30 minutes of occlusion to simulate typical delay before seeking medical attention. Eighteen animals were studied under normothermic conditions with reperfusion after an additional 40 minutes (the porcine equivalent of a 120-minute clinical FMC to reperfusion time) and 18 were treated with hypothermia but not reperfused until another 80 minutes (clinical equivalent of 240 minutes). Primary outcome was myocardial infarct size (infarct/area at risk [AAR]) at 24 hours. The two groups differed in systemic temperature at the time of reperfusion (39.1°C ± 1.0°C vs. 35.5°C ± 0.7°C; p < 0.0001). Myocardial infarct size was not significantly different despite the longer time to reperfusion in those treated with hypothermia (60.6% ± 12% of the AAR [normothermic] vs. 65.8% ± 11.8% of the AAR [hypothermic]; p = 0.39). Rapid induction of MTH during an anterior STEMI made it possible to extend the FMC to reperfusion time by the equivalent of an extra two clinical hours (120-240 minutes) without increasing the myocardial infarct size. This strategy could allow more STEMI patients to receive PPCI rather than the less effective intravenous fibrinolysis.

Keywords: PPCI; STEMI; fibrinolysis; infarct size; mild hypothermia.