INDUCTION OF HYPERCONTRACTILITY IN HUMAN CEREBRAL-ARTERIES BY REWARMING FOLLOWING HYPOTHERMIA - A POSSIBLE ROLE FOR TYROSINE KINASE

Induction of hypothermia is used routinely in neurosurgical and cardio vascular operations to protect the brain from ischemic insult. However , despite a plethora of experimental evidence supporting the use of hy pothermia to protect the brain from ischemia, clinical experience usin g deliberate hypothermia in humans has not shown a convincing benefit. The authors tested the hypothesis that hypothermia and rewarming alte r tone in human cerebral Vessels and may interfere with cerebral perfu sion in the setting of deliberate hypothermia. They examined human cer ebral arteries during hypothermia (32 degrees C and 17 degrees C) and during rewarming to delineate the direct effects of cooling and rewarm ing on cerebrovascular tone. Artery segments obtained from autopsy mat erial and from specimens excised at elective temporal lobectomies were tested in tissue baths using isometric tension measurements. Temperat ure-induced changes in vascular tone were measured and quantified with respect to contractile responses to serotonin (5-HT; 10(-6) M). Cooli ng induced mild relaxation in cerebral vessels (-38 +/- 12% 5-HT respo nse in 50 vessels from autopsy speci mens, -69 +/- 10% 5-HT response i n 51 Vessels from lobectomy specimens). On rewarming, Vessels contract ed significantly beyond their baseline tone (108 +/- 18% 5-HT response in 50 vessels from autopsy specimens, 42 +/- 12% 5-HT response in 51 vessels from lobectomy specimens). Rewarming-induced hypercontractilit y was inhibited by the tyrosine kinase inhibitor genistein (-5 +/- 7% vs. 70 +/- 23% 5-HT response, genistein vs. control, 14 segments, p < 0.05) and enhanced by the tyrosine phosphatase inhibitor sodium orthov anadate (339 +/- 54% vs. 104 +/- 20% 5-HT response, sodium orthovanada te vs. control, five segments, p < 0.05), indicating a possible role f or tyrosine kinase activation in the rewarming-induced contraction.