Does mild hypothermia protect against reperfusion injury? The debate continues

Abstract

Mild hypothermia (32-35°C) 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 Götberg 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. Götberg's new data are encouraging, but it is questioned whether this is the correct time to conduct a new large-scale clinical trial.In 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 4°C (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 (32-35°C) 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 32°C because lowering the temperature below 30°C is life-threatening. But 32°C 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. We have found that the magnitude of the protection depends upon how much of R. Tissier INSERM, Unité 955,

Fundamental research progress of mild hypothermia in cerebral protection

“…However, after re-warming the apoptotic speed rebounds rapidly. Therefore, the time window for mild hypothermia beginning should be actively sought (Tissier et al 2011). One research found that pre-operation hypothermia could reduce the damage of neuron and glia in the reperfusion phase of ischemia/reperfusion brain injury (Yokobori et al 2013).…”

Mild hypothermia during global cardiac ischemia opens a window of opportunity to develop heart donation after cardiac death

“…In this particular DCD setting (planned withdrawal of treatment), currently available cooling techniques could effectively reduce cardiac temperature by a few degrees prior to the onset of cardiac ischemia. Secondly, given that multiple methods to rapidly induce mild hypothermia are currently being developed and tested , our results highlight the potential need for rapid cooling techniques in the context of DCD.…”

A Review of Mild Hypothermia as an Adjunctive Treatment for ST-Elevation Myocardial Infarction

“…The combined results of these studies demonstrate an excellent correlation between the duration of cooling during ischemia and infarct size (Tissier et al, 2011a(Tissier et al, , 2011b. In a review by Tissier and coworkers, the results of 16 studies on the effect of hypothermia during ischemia are summarized in a structured table.…”

“…The effects of hypothermia immediately before and after reperfusion have been examined in other animal studies, but the cooling methods were often too slow to achieve therapeutic temperatures before reperfusion (Maeng et al, 2006), or the statistical significance was only borderline (Otake et al, 2007). Tissier and coworkers applied rapid liquid ventilation cooling in a rabbit model just before reperfusion and succeeded in reaching therapeutic temperatures without observing any effect on infarct size (Tissier et al, 2007(Tissier et al, , 2011b. In contrast, a reduction in infarct size was found in another rabbit study when hypothermia was initiated 5 minutes before reperfusion (Kanemoto et al, 2009).…”