Hypothermia extends the cardioprotection by ischaemic preconditioning to coronary artery occlusions of longer duration

Doel, M. A. van den; Gho, B. C. G.; Duval, Stanley Y; Schoemaker, Regien G.; Duncker, Dirk J.; Verdouw, Pieter D.

doi:10.1016/s0008-6363(97)00222-8

Cited by 58 publications

(53 citation statements)

References 19 publications

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“…Few explanations come to mind that might explain the apparent discrepancy between the present results and the previous ones that failed to show any effect of cooling against reperfusion injury [5,10,17,21,27]. In their report, Götberg et al [7] induced cooling by endovascular cooling and intravenous infusion of cold saline.…”

contrasting

confidence: 76%

“…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].…”

mentioning

confidence: 78%

“…1, target hypothermia was already present at reperfusion. A lack of protection of mild hypothermia when initiated only at reperfusion has been shown in many other experimental reports [5,10,17,21,27] and would suggest that hypothermia has no effect on reperfusion injury per se. This is an important point because it is not easy to cool the human body quickly.…”

mentioning

confidence: 82%

“…1. The infarct size reduction elicited by cooling to 32°C decreases as the delay between the onset of a 30-min period of ischemia and the time when target cooling is finally achieved increases [9,10,18,26,27]. When hypothermia began at the 25th min of ischemia, reduction in infarct size was no longer significant [27].…”

mentioning

confidence: 97%

“…The large volume of saline that the pigs received could account for the difference. Previous negative studies used cooling methods not affecting the blood volume, such as topical cooling [10], extracorporeal blood cooling [18] or total liquid ventilation [27]. But infusing cold saline alone did not cool as well nor was it protective suggesting that the temperature rather than volume was the critical factor.…”

mentioning

confidence: 99%

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Does mild hypothermia protect against reperfusion injury? The debate continues

2011

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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,

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confidence: 76%