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(Stroke. 1995;26:1273-1278.)
© 1995 American Heart Association, Inc.

Articles

Deep Hypothermia Diminishes the Ischemic Induction of Heat-Shock Protein-72 mRNA in Piglet Brain

Ellen G. Shaver, MD; Frank A. Welsh, PhD; Leslie N. Sutton, MD; Gerardo Mora, MD; Laura M. Gennarelli, BS Carole R. Norwood, PhD

From the Division of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia (E.G.S., F.A.W.); and the Division of Neurosurgery (L.N.S., L.M.G.) and the Cardiac Surgical Research Laboratories (G.M., C.R.N.), The Children's Hospital of Philadelphia (Pa).

Correspondence to Dr Frank A. Welsh, 313 Stemmler Hall, 36th and Hamilton Walk, Philadelphia, PA 19104.

Background and Purpose Expression of the 72-kD heat-shock protein (HSP72) has served as a useful indicator of ischemic stress after cerebral ischemia. Moderate hypothermia (30°C) has been reported to block the induction of HSP72 after a brief episode of forebrain ischemia. The objective of the present study was to examine the effects of deep hypothermia (15°C) on expression of HSP72 after a prolonged period of cerebral ischemia.

Methods Piglets, 19 to 23 days old, were placed on cardiopulmonary bypass, and brain temperature was lowered to 23°C (n=9) or 15°C (n=9) before circulatory arrest for 1 hour. In an additional group of animals (n=5), the temperature was lowered to 29°C before arrest for 45 minutes. All animals were reperfused at 37°C for 2 hours, and the regional expression of HSP72 mRNA was assessed using in situ hybridization.

Results After ischemia at 15°C, expression of HSP72 mRNA was limited to a few scattered regions of cerebral cortex; the percentage of cortex exhibiting HSP72 mRNA was 23±7% (mean±SEM). Ischemia at 23°C triggered expression of HSP72 mRNA in a significantly larger portion of the cortex (68±8%, P<.001). Ischemia at 29°C failed to induce substantial expression of HSP72 mRNA in the cerebral cortex.

Conclusions These results suggest that, relative to ischemia at 23°C, deep hypothermia (15°C) diminishes ischemic alterations leading to induction of HSP72 mRNA. The lack of cortical expression of HSP72 mRNA following ischemia at 29°C may be secondary to inadequate recovery of energy metabolism.

Key Words: cardiopulmonary bypass • cerebral ischemia • heat-shock proteins • hypothermia • pigs

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