Abstract 11263: Delayed Hypothermia Reduces the No-Reflow Phenomenon Independently of Effect on Infarct Size: Evidence that Microvascular Damage Represents True Reperfusion Injury
Hypothermia initiated during myocardial ischemia limits necrosis and no-reflow. However, studies from our lab and others have shown that when hypothermia is started after coronary artery reperfusion, it is ineffective in reducing necrosis. Here we tested the specific effects on microvascular damage when hearts were treated with hypothermia, initiated well after coronary artery reperfusion.
Methods: Anesthetized, open-chest rabbits were subjected to 30 min coronary artery occlusion and a total of 3 hrs reperfusion. After 30 min of reperfusion, hearts were randomly treated with topical myocardial hypothermia for 1 hr (myocardial temperature ∼32.5 ºC, n=12, H) or hearts remained normothermic (∼38ºC, n=12, N). Risk zone was measured by blue pigment, anatomic no-reflow area using Thioflavin S, a marker that stains viable endothelium of the vasculature, and necrosis by triphenyltetrazolium chloride.
Results: The ischemic risk zone was comparable in both groups (22% of left ventricle in H and 25% in N, p=ns). As we and others have observed, hypothermia started during reperfusion failed to reduce infarct size (33± 3% of risk zone in H vs. 30 ± 4 % in N, p = 0.58). In contrast, no-reflow was significantly reduced in hearts treated with hypothermia by 30% (Figure, 55±6% of the necrotic region in H vs. 79±6% in N, p = .008), and there was a significant effect of hypothermia on the relationship between the extent of the no-reflow zone and that of the necrotic zone (ANCOVA, p = 0.011). Histological examination revealed endothelial blebs, erythrocyte congestion and microvascular hemorrhage within no-reflow areas.
Conclusions: To our knowledge, this is the first demonstration that modest myocardial hypothermia reduces no-reflow injury even when cooling is initiated too late to reduce myocyte necrosis. These data suggest that microvascular injury represents true reperfusion injury, and that the microvasculature is especially receptive to the salvaging properties of hypothermia.
- © 2012 by American Heart Association, Inc.