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OBJECTIVE:: Several cooling methods have been investigated for inducing mild hypothermia (3336C) after cardiac arrest, brain trauma, or stroke. To achieve its best effect, therapeutic hypothermia has to be applied very early after the ischemic insult; otherwise, the beneficial effect would be diminished or even abrogated. The aim of this study was to investigate the effectiveness and safety of extracorporeal venovenous cooling as compared with endovascular cooling. DESIGN:: Swine were cooled in a randomized crossover design from 38C to 33C brain temperature, either with extracorporeal venovenous cooling or with endovascular cooling. SETTING:: Laboratory investigation. SUBJECTS:: Six swine of human size (85 to 101 kg). INTERVENTIONS:: Swine were randomly cooled with the first device, and after achieving the target brain temperature, re-warmed via the same technique and with heating lamps to baseline temperature. Then the other catheter was inserted and cooling was performed with the second device. MEASUREMENTS:: Brain, pulmonary artery and tympanic temperature, blood pressure, and heart rate were recorded continuously. Laboratory samples, including free hemoglobin, were taken at predefined temperature points during cooling. Comparisons between and within (baseline vs. 33C) the treatment groups were performed with the paired Students t-test. MAIN RESULTS:: The time needed to reduce brain temperature from 38.0C to 33.0C was 41 17 mins with venovenous cooling and 126 37 mins with endovascular cooling (p = .001). Heart rate and mean arterial pressure decreased moderately during cooling and were significantly lower at 33C than at baseline in both groups, without differences between groups. None of the swine developed significant hemolysis, arrhythmias, or bleeding. CONCLUSIONS:: Extracorporeal venovenous cooling was an effective and safe method to rapidly induce therapeutic mild hypothermia in human-sized swine. It seems to be promising for further application and investigation in patients. [ABSTRACT FROM AUTHOR]