Does mild hypothermia protect against reperfusion injury? The debate continues

Mild hypothermia (32–35C) salvages ischemic myocardium and reduces infarct size in hearts undergoing ischemia/reperfusion. It is clear that a cardioprotective effect is evident when the heart is cooled during ischemia, and the protection is greater as the duration of normothermic ischemia is increasingly limited. The effect of cooling just before and at reperfusion is more controversial. Multiple experimental studies have revealed no effect of mild hypothermia on myocardial infarction when cooling was initiated in the waning minutes of ischemia. But Go¨tberg et al. have demonstrated a small effect in pigs cooled with cold intravenous saline and a venous thermode, although the effect of cooling during ischemia continued to be more prominent. Clinical studies have been disappointing, and possible explanations are offered. Go¨tberg’s new data are encouraging, but it is questioned whether this is the correct time to conduct a new large-scale clinical trialIn animal models of coronary artery occlusion/reperfusion cardiac temperature is known to be a major determinant of infarct extension, along with collateral blood flow and risk zone size [2, 4, 23]. Cooling to 4C (deep hypothermia) has long been used to protect the heart during open heart surgery and transplantation. In those cases, the heart is quiescent and metabolism is greatly curtailed. What is surprising is that mild hypothermia (32–35C) is also quite protective. Mild hypothermia has the advantage that, under those conditions, the heart beats normally which allows simple whole body cooling without the need for cardiovascular support. Chien et al. [2] reported that for each degree C decrement of the core temperature in rabbits undergoing 30 min of ischemia followed by reperfusion infarct size was reduced by an average of 8% of the risk zone. When induced during the ischemic process, mild hypothermia is, therefore, one of the most potent cardioprotective strategies yet to be identified. Studies of therapeutic whole body cooling have limited the range of cooling to be no lower than 32C because lowering the temperature below 30C is life-threatening. But 32C is already quite protective [18]. This protective effect of whole body cooling against infarction has been reported for many experimental animal species (pigs [3, 4, 21, 22], rats [28], rabbits [2, 9, 12, 13, 18, 27], dogs [23]). Mild hypothermia also attenuates no-reflow [1, 5, 9], postischemic left ventricular dysfunction [26], and remodeling [14]. As emphasized by two recent reviews [11, 25], the evidence for a cardioprotective effect of therapeutic mild hypothermia against ischemic injury is very strong. An important consideration in therapeutic hypothermia is not only its dose (depth of cooling) but also its schedule. All investigators would probably agree that hypothermia is most protective when present during ischemia.Wehave found that the magnitude of the protection depends upon how much of