• Yuji Ueda, Eiichi Suehiro, Enoch P Wei, Hermes A Kontos, and John T Povlishock.
• Department of Anatomy and Neurobiology, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, VA 23298-0709, USA.
• Stroke. 2004 Feb 1;35(2):601-6.

Background And PurposeRecently, we focused on the cerebrovascular protective effects of moderate hypothermia after traumatic brain injury, noting that the efficacy of posttraumatic hypothermia is related to the rate of posthypothermic rewarming. In the current communication, we revisit the use of hypothermia with varying degrees of rewarming to ascertain whether, in the normal cerebral vasculature, varying rates of rewarming can differentially affect cerebrovascular responsiveness.MethodsPentobarbital-anesthetized rats equipped with a cranial window were randomized to 3 groups. In 1 group, a 1-hour period of hypothermia (32 degrees C) followed by slow rewarming (over 90 minutes) was used. In the remaining 2 groups, either a 1- or 2-hour period of hypothermia was followed by rapid rewarming (within 30 minutes). Vasoreactivity to hypercapnia and acetylcholine was assessed before, during, and after hypothermia. Additionally, the vascular responses to sodium nitroprusside (SNP) and pinacidil, a K(ATP) channel opener, were also examined.ResultsHypothermia itself generated modest vasodilation and reduced vasoreactivity to all utilized agents. The slow rewarming group showed restoration of normal vascular responsivity. In contrast, hypothermia followed by rapid rewarming was associated with continued impaired responsiveness to acetylcholine and arterial hypercapnia. These abnormalities persisted even with the use of more prolonged (2-hour) hypothermia. Furthermore, posthypothermic rapid rewarming impaired the dilator responses of SNP and pinacidil.ConclusionsPosthypothermic rapid rewarming caused cerebral vascular abnormalities, including a diminished response to acetylcholine, hypercapnia, pinacidil, and SNP. Our data with acetylcholine and SNP suggest that rapid rewarming most likely causes abnormality at both the vascular smooth muscle and endothelial levels.

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