Hypothermia as an adjunctive therapy in Acute Myocardial Infarction and Cardiogenic Shock

Sammanfattning: INTRODUCTION: Reperfusion therapy in patients with an ongoing ST-elevation myocardial infarction (STEMI) is to re-establish coronary flow in the epicardial arteries as soon as possible in order to reduce infarct size and associated complications. Hypothermia has in experimental studies been shown to reduce infarct size. Clinical trials, however, have not been able to show this effect, possibly because a therapeutic temperature was not reached before reperfusion in the majority of the patients allocated to hypothermia treatment. We aimed to evaluate if hypothermia initiated before reperfusion would reduce infarct size. Furthermore, a protocol utilising a combination of an infusion of cold saline and endovascular cooling catheter was evaluated. Finally, the effects of hypothermia in cardiogenic shock were investigated. MATERIAL and METHODS: For paper I-III, an experimental closed chest porcine model was used. Ischemia was induced by occlusion of the LAD using a PCI-balloon. Different hypothermia protocols using cold saline, endovascular cooling in combination or alone were tested. Infarct size and microvascular obstruction were evaluated using ex-vivo MRI. In paper III, endovascular cooling alone was investigated in a porcine model of cardiogenic shock. In paper IV, the safety and feasibility of the hypothermia protocol utilised in paper I, II was tested in a clinical trial in patients with STEMI. RESULTS: Paper I: Combination hypothermia (a combination of an infusion of cold saline and endovascular cooling catheter), if initiated before reperfusion reduced infarct size by 39%, and abolished microvascular obstruction compared to normothermia. Furthermore, the hypothermia protocol achieved a reduction in core body temperature to < 35°C in <10 min. However, hypothermia induced at the onset of reperfusion reduced microvascular obstruction by 66%, but did not affect infarct size. In Paper II, combination hypothermia reduced infarct size by 18% and microvascular obstruction was virtually abolished despite prolonged ischemic time compared to normothermia. Furthermore, an infusion of cold saline alone did not reduce infarct size, but reduced microvascular obstruction by 74%. Prolonged post-reperfusion hypothermia did not offer any additional. In Paper III, endovascular hypothermia improved survival (8/8 vs. 3/8, hypothermia vs. control), improved hemodynamic parameters, and reduced acidosis in cardiogenic shock. Paper IV: Combination hypothermia in patients with STEMI was able to safely reach a core body temperature of < 35°C before reperfusion without delaying primary PCI, and resulted in a 38% reduction in infarct size. CONCLUSIONS: In order for hypothermia treatment to reduce infarct size, it needs to be initiated before reperfusion. The results indicate that it is safe and clinically feasible to induce hypothermia by using a combination of cold saline infusion and endovascular cooling prior to reperfusion in awake STEMI patients without delaying time to reperfusion. Furthermore, hypothermia improves outcome in cardiogenic shock. Larger randomized clinical trials are needed to verify these findings and to assess possible long term clinical benefit for the patients.