Delayed therapeutic hypothermia protects against the myocardial no-reflow phenomenon independently of myocardial infarct size in a rat ischemia/reperfusion model.

BACKGROUND: Adjunctive therapies, given in addition to reperfusion to reduce myocardial infarct size, have been disappointing based on clinical trials. New therapeutic targets independent of infarct size modification are needed. The no-reflow phenomenon occurs commonly after the infarct-related coronary artery is opened and predicts poor clinical outcome. We investigated the effects of a single application of delayed (post-reperfusion) therapeutic hypothermia (TH) in a rat model of coronary artery occlusion/reperfusion. METHODS: Rats were subjected to 60min of coronary artery occlusion followed by 3h of reperfusion. Rats were divided into normothermic (n=5) and TH (n=5) groups. In the TH, hypothermia was initiated at 1min after coronary artery reperfusion by pumping room-temperature (22°C) saline into and out of the thoracic cavity for 1h. This decreased intrathoracic temperature to around 26°C within 12min. At 3h after reperfusion, hearts were excised for infarct size and no-reflow zone measurement. RESULTS: Ischemic risk area and infarct size were similar between the 2 groups. No-reflow area (expressed as % of risk area) was significantly reduced in TH group (18.0±4.4%) compared with normothermic group (39.5±2.9%,P=0.005). When expressed as % of necrotic area, no-reflow area was reduced by more than half in TH group (25.5±6.4%) versus innormothermic group (54.4±5.3%,P=0.01). CONCLUSIONS: In this preliminary study, hypothermia initiated after reperfusion following 60min of coronary artery occlusion had no effect on infarct size yet substantially reduced the extent of no-reflow.