Delayed Treatment With Hypothermia Protects Against the No‐Reflow Phenomenon Despite Failure to Reduce Infarct Size

BACKGROUND Many studies have shown that when hypothermia is started after coronary artery reperfusion (CAR), it is ineffective at reducing necrosis. However, some suggest that hypothermia may preferentially reduce no-reflow. Our aim was to test the effects of hypothermia on no-reflow when initiated close to reperfusion and 30 minutes after reperfusion, times not associated with a protective effect on myocardial infarct size. METHODS AND RESULTS Rabbits received 30 minutes coronary artery occlusion/3 hours CAR. In protocol 1, hearts were treated for 1 hour with topical hypothermia (myocardial temperature ≈32°C) initiated at 5 minutes before or 5 minutes after CAR, and the results were compared with a normothermic group. In protocol 2, hypothermia was delayed until 30 minutes after CAR and control hearts remained normothermic. In protocol 1, risk zones were similar and infarct size was not significantly reduced by hypothermia initiated close to CAR. However, the no-reflow defect was significantly reduced by 43% (5 minutes before CAR) and 38% (5 minutes after CAR) in hypothermic compared with normothermic hearts (P=0.004, ANOVA, P=ns between the 2 treated groups). In protocol 2, risk zones and infarct sizes were similar, but delayed hypothermia significantly reduced no-reflow in hypothermic hearts by 30% (55±6% of the necrotic region in hypothermia group versus 79±6% with normothermia, P=0.008). CONCLUSION These studies suggest that treatment with hypothermia reduces no-reflow even when initiated too late to reduce infarct size and that the microvasculature is especially receptive to the protective properties of hypothermia and confirm that microvascular damage is in large part a form of true reperfusion injury.