Abstract OBJECTIVES: We tested whether total liquid ventilation (TLV) can be used to rapidly cool and protect the infarcting heart. BACKGROUND: Decreasing myocardial temperature during ischemia is a powerful cardioprotective strategy, but clinical application has been impaired by lack of practical methodology to quickly cool the heart. METHODS: We performed 30-min coronary artery occlusion/3-h reperfusion in rabbits. Upon occlusion, rabbits underwent either oxygen (Gas), normothermic liquid (Liquid Warm), or cold liquid (Liquid Cool) ventilation. RESULTS: Left atrial chamber temperature decreased to 32.4 degrees +/- 0.2 degrees C within 5 min of onset of cold TLV. Blood gases were within acceptable limits during TLV. In the Liquid Warm group, perfluorocarbon inhalation did not alter infarct size compared with Gas (37.7 +/- 1.3% and 42.5 +/- 4.9% of risk zone, respectively). However, infarction was significantly reduced in the Liquid Cool group (4.0 +/- 0.5%). Cooling only during the initial 30 min of reperfusion did not reduce infarction. CONCLUSIONS: Total liquid ventilation can elicit rapid cardioprotective cooling during ischemia.