Mild hypothermia as a cardioprotective approach for acute myocardial infarction: laboratory to clinical application.

In many animal models, mild therapeutic hypothermia is a powerful intervention, reducing myocardial infarct size, reducing the no-reflow phenomenon, and improving healing after infarction. Cooling in these models has been produced by various means including whole-body hypothermia, synchronized hypothermic coronary venous retro-perfusion, heat exchangers, and regional hypothermia targeting the heart alone. However, in humans, the most widely used techniques are surface cooling and cooling by endovascular heat-exchange catheters. The reduction in temperature necessary to produce cardioprotection is mild (32-34°C), appears to have no detrimental effects on left ventricular function or regional myocardial blood flow, and may improve microvascular reflow to previously ischemic heart tissue. It has been shown in experimental and clinical studies that for therapeutic hypothermia to be effective it must be (1) initiated as early as possible after the onset of ischemia and (2) initiated before reperfusion. This may require initiation of hypothermia in the ambulance, well before mechanical reperfusion occurs. The mechanisms of protection produced by hypothermia have yet to be conclusively determined but may include a decrease in tissue metabolic rate, preservation of high energy phosphates, a reduction in tissue apoptosis or induction of heat shock proteins.