Novel method for inducing rapid, controllable therapeutic hypothermia in rats using a perivascular implanted closed-loop cooling circuit

Abstract

BackgroundHypothermia is the most potent protective therapy available for cerebral ischemia. In experimental models, cooling the brain even a single degree Celsius alters outcome after global and focal ischemia. Difficulties translating therapeutic hypothermia to patients with stroke or after cardiac arrest include: uncertainty as to the optimal treatment duration; best target-depth temperature; and longest time delay after which therapeutic hypothermia won’t benefit. Recent results from human clinical trials suggest that cooling with surface methods provides insufficient cooling speed or control over target temperature. Comparison with existing methodsAvailable animal models incorporate surface cooling methods that are slow, and do not allow for precise control of the target temperature. New methodTo address this need, we developed a rapid, simple, inexpensive model for inducing hypothermia using a perivascular implanted closed-loop cooling circuit. The method allows precise control of the target temperature. ResultsUsing this method, target temperature for therapeutic hypothermia was reached within 13±1.07min (Mean±SE). Once at target, the temperature was maintained within 0.09°C for 4h. ConclusionsThis method will allow future experiments to determine under what conditions therapeutic hypothermia is effective, determine the optimal relationship among delay, duration, and depth, and provide the research community with a new model for conducting further research into mechanistic questions underlying the efficacy of therapeutic hypothermia.