Induction of hypercontractility in human cerebral arteries by rewarming following hypothermia: a possible role for tyrosine kinase

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Abstract
Induction of hypothermia is used routinely in neurosurgical and cardiovascular operations to protect the brain from ischemic insult. However, despite a plethora of experimental evidence supporting the use of hypothermia to protect the brain from ischemia, clinical experience using deliberate hypothermia in humans has not shown a convincing benefit. The authors tested the hypothesis that hypothermia and rewarming alter tone in human cerebral vessels and may interfere with cerebral perfusion in the setting of deliberate hypothermia. They examined human cerebral arteries during hypothermia (32 degrees C and 17 degrees C) and during rewarming to delineate the direct effects of cooling and rewarming on cerebrovascular tone. Artery segments obtained from autopsy material and from specimens excised at elective temporal lobectomies were tested in tissue baths using isometric tension measurements. Temperature-induced changes in vascular tone were measured and quantified with respect to contractile responses to serotonin (5-HT; 10(-6) M). Cooling induced mild relaxation in cerebral vessels (-38 +/- 12% 5-HT response in 50 vessels from autopsy specimens, -69 +/- 10% 5-HT response in 51 vessels from lobectomy specimens). On rewarming, vessels contracted 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 hypercontractility 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 orthovanadate (339 +/- 54% vs. 104 +/- 20% 5-HT response, sodium orthovanadate vs. control, five segments, p < 0.05), indicating a possible role for tyrosine kinase activation in the rewarming-induced contraction.