Hypothermia-induced ischemic tolerance.

Delayed resistance to ischemic injury can be induced by a variety of conditioning stimuli. This phenomenon, known as delayed ischemic tolerance, is initiated over several hours or a day, and can persist for up to a week or more. The present paper describes recent experiments in which transient hypothermia was used as a conditioning stimulus to induce ischemic tolerance. A brief period of hypothermia administered 6 to 48 hours prior to focal ischemia reduces subsequent cerebral infarction. Hypothermia-induced ischemic tolerance is reversed by 7 days postconditioning, and is blocked by the protein synthesis inhibitor anisomycin. Electrophysiological studies utilizing in vitro brain slices demonstrate that hypoxic damage to synaptic responses is reduced in slices prepared from hypothermia-preconditioned animals. Taken together, these findings indicate that transient hypothermia induces tolerance in the brain parenchyma, and that increased expression of one or more gene products contributes to this phenomenon. Inasmuch as hypothermia is already an approved clinical procedure for intraischemic and postischemic therapy, it is possible that hypothermia could provide a clinically useful conditioning stimulus for limiting injury elicited by anticipated periods of ischemia.